Herbal and Nutritional Supplements for Painful Conditions

Herbs and supplements are widely used by patients in pain. Throughout this chapter, mechanisms of action and efficacy, dosing, and safety information will be provided for each herb, supplement, and natural product for the pain syndromes for which research literature supports their use. For herbs, the medicinal portion of the plant will also be given because different parts of a plant may have different constituents and clinical effects. This chapter is meant to provide an overview, and practitioners not already trained in natural medicine should seek additional education to become proficient in the use of natural products.

Natural substances offer many potential benefits for helping treat patients with pain. First, they often have long histories of use (thousands of years in some cases; the Ebers Papyrus, arguably the oldest book in the world, consists of a materia medica of traditional Egyptian medicine ), and one could argue these substances are among the best tested and most “evidence-based” medicines available. Second, they are largely nontoxic, although there are exceptions. One study found that over a 10-year period, only two deaths in the United States could be linked to herbal medicines. Third, they are often cost effective, again, with exceptions. Finally, they act on multiple pathways, some of which are not addressed by any other existing therapies. Study of the mechanism of action of some natural treatments has led to breakthroughs in the understanding of pain pathophysiology and to the development of entirely new categories of medications. For example, investigation of capsaicin brought about enhanced understanding of vanilloid receptors, TRPV1, unmyelinated C fibers, substance P, and novel topical treatments for pain syndromes.

Western Herbal Medicine: Complexity and Synergy

Herbs have been an important part of Western medicine for thousands of years. Herbs contain hundreds of different compounds, and traditional medicine theorizes that the constituents of medicinal plants act synergistically. Many studies support that complex herbal extracts often have effects that are distinct and/or greater than those of their single isolated constituents.

In some cases, isolated compounds or highly refined extracts with just a few constituents such as silymarin, a complex of three flavonoligans from Silybum marianum (milk thistle) seed, or curcumin, a mixture of three resinous polyphenols from Curcuma longa (turmeric) rhizome, are used clinically. It is not clear if these offer advantages over more complex, less concentrated extracts, given a near total lack of comparative studies, but such extracts do satisfy the demand for uniformity, simplicity, and patentability prevalent in a market-driven health care system and society. Throughout this chapter, both refined and crude herbal extracts will be listed for completeness, although often it is unknown which form is superior ( Table 20-1 ).

Table 20-1

Summary of Herbs and Supplements Used for Treatment of Pain

Name Indications Dosages Cautions Contraindications
Antiinflammatory herbs and supplements
Curcuma longa (Turmeric) Osteoarthritis Rheumatoid arthritis 1-3 g powdered tuber three times per day, or 1-3 mL liquid extract five times per day; 500-2000 mg curcumin tid Turmeric (but not curcumin) contains oxalates and should be taken with high-fiber or high-calcium foods to avoid exacerbation of kidney stones Doses greater than 15 g per day in patients who take anticoagulants; biliary obstruction

  • General inflammation

  • Exercise recovery

  • Osteoarthritic pain

  • Wound healing

500-2000 mg three or more times per day (potency of 2400 mcu or 3200 gdu per 1000 mg) Must not be taken with food Because bromelain inhibits synthesis of fibrinogen and increases fibrinolytic activity, it theoretically increases the risk of bleeding
Omega-3 oils

  • Antiinflammatory

  • Exercise tolerance

  • Rheumatoid arthritis

  • Osteoarthritis

6-9 g fish oil providing a minimum of 1.8 g EPA per day. At least 3 months of treatment is usually required for a therapeutic effect May cause bruising in some individualsData are varied whether omega-3 fatty acids inhibit clot formation Some sources give a contraindication for omega-3 fats presurgically because of their possible anticoagulant effects
Angelica sinensis (Dang gui, tang kui)

  • General pain

  • Dysmenorrhea

4.5-15 g dried root per day in divided doses In traditional Chinese medicine, it is used after the first trimester of pregnancy, although its use in pregnancy is contraindicated altogether in some other sources

  • During pregnancy with a history of habitual miscarriageTraditionally not used in cases of diarrhea or acute viral infection

  • In one study, Angelica potentiated anticoagulant effects of warfarin

  • Theoretically, it may interact with other anticoagulants as well

Zingiber officinalis (Ginger)

  • Inflammatory pain

  • Migraine

  • Dysmenorrhea

  • Osteoarthritis

  • Rheumatoid arthritis

  • Myalgia

250 mg/1 g encapsulated, one to four times per day; eaten with food as tolerated
Harpagophytum procumbens (Devil’s claw) Low back pain

  • Standardized extract providing 50-100 mg harpagosides per dayTincture (1:2-1:5): 4-5 mL three times per day

  • Liquid extract (1:1): 3-4 mL three times daily

Harpagophytum may potentiate effects of warfarin Contraindicated in hyperchlorhydria, acute peptic ulcers, and acute diarrhea
Boswellia serrata (Frankincense)

  • Osteoarthritis

  • Collagenous colitis

150-400 mg boswellic acid taken three times daily Caution: may cause contact dermatitis or mild diarrhea or urticaria
Tanacetum parthenium (Feverfew) Migraine

  • 25-225 mg per day

  • Tincture (1:2 or 1:3) 3-5 mL three times per day for prevention and up to 10-12 mL five times a day for acute treatmentPatients may chew 1-3 fresh leaves daily for migraine prophylaxis, although mouth ulcers are occasionally reported with this administration

Caution in allergy to members of the Asteraceae (Compositae), and during pregnancy because it may stimulate uterine contraction
Centrally-acting analgesics
Corydalis yanhusuo (Yanhusuo)

  • General pain

  • Cancer pain

  • Dysmenorrhea

Crude herb, decocted: 4.5-12 g per day, divided doses
Tincture: 0.25-1 mL three times daily
In Chinese medicine, this herb is generally contraindicated during pregnancy
Cannabis sativa (Marijuana)

  • Postsurgical pain

  • Neuropathic pain

  • Sleep improvement

  • Rheumatoid arthritis

  • Severe pain/adjunct to opiate treatment

  • Further study is needed to determine dosage for most conditions

  • A therapeutic window should be established because Cannabis may cause hyperalgesia at high doses

May worsen hepatic fibrosis in patients with Hepatitis C Use of Cannabis, especially in adolescents and people at risk for mental illness, may be related to onset of psychological diseases such as psychosis or schizophrenia
Hypericum perforatum (St. John’s Wort)

  • Otitis media

  • Burning mouth syndrome

  • Neuropathy

  • Tincture (1:5): 2-4 mL three times per day

  • Decoction: 2-4 g dried herb taken three times per dayStandardized extract: 300 mg tid providing 0.3% hypericin and 5% hyperforin

  • Due to its upregulatory effects on some cytochrome P450 enzymes Hypericum reduces serum levels of certain drugs

  • Drugs for which interaction has been demonstrated include anti-HIV protease inhibitors, cyclosporine, atorvastatin, simvastatin, finasteride, and digoxin

  • It may also decrease efficacy of oral contraceptivesAt extremely high doses, Hypericum may cause photosensitivity in light-skinned individuals

Bryonia alba (White bryony) (1:10) one drop in approximately 120 mL three times daily
Capsicum frutescens (Cayenne)

  • Postherpetic neuralgia

  • Diabetic neuropathy

  • Arthritis

  • Mouth pain following chemotherapy and radiation

  • Postmastectomy pain

  • Trigeminal neuralgia

  • Cluster headaches

Typically requires application two or three times a day or pain sensation may return

  • Capsaicin causes topical irritation (usually minor) on initial application, but this almost always passes with frequent use

  • To achieve a therapeutic effect, patients must often overcome an initial period of discomfort before desensitization has occurred

Urtica dioica (Stinging nettle) Joint pain

  • Apply fresh leaf topically to affected area for approximately 30 seconds two or three times.

  • Repeat as needed

Theoretically, internal use may decrease efficacy of warfarin due to nettle leaf’s substantial vitamin K content
Symphytum officinale (Comfrey) OsteoarthritisBack pain 1-2 g topically three to five times per day uPA-containing extracts pose a minor risk of hepatotoxicity and carcinogenicity, although these alkaloids show only minimal transdermal absorbtionuPA-free extracts pose no such risk
Arnica montana Bruising Osteoarthritis Apply topically three to five times per day Not to be taken internally or applied to broken skin or near the mouthHomeopathic topical preparations do not pose risk of toxicity in pregnancy Contraindicated in pregnancy in physiologic doses
Dimethyl sulfoxide (DMSO)

  • As a carrier for other analgesics

  • CRPS

Applied topically five times per day May cause skin irritation
Echinacea spp. (Purple coneflower) Pharyngeal pain Throat spray: Two puffs every two hours for duration of symptomsTincture: 1-5 mL in water as a gargle Contraindication in allergy to members of the Asteraceae (Compositae) family
Salicylate-containing herbal medicines
Salix alba (White willow)

  • Low back pain

  • Osteoarthritis

  • Standardized extract providing 120-240 mg salicylateFluid extract (1:1): 2-4 mL three times daily

  • Fluid extract (1:2): 3-5 mL three to five times per day

Salicylate allergy
Hypnotic analgesics
Valeriana officinalis (Valerian) Extract 1:2-1:3: 3-5 mL three times daily with 5-10 mL at bedtime Occasionally, Valeriana may cause agitation
Piscidia spp. (Jamaican dogwood)

  • Crude root bark (dried): 2-4 g three times daily

  • Aqueous extract: (1:2) 1-2 mL three times per dayTincture: (1:5) 5-15 mL three times per day

Dosing simultaneously with other sedative therapies because Piscidia may amplify these effects Pregnancy, bradycardia and cardiac insufficiency
Eschscholtzia californica (California poppy) Tincture (1:2): 1-2 mL three times per day Contraindicated in pregnancy; animal studies indicate that cryptopine causes uterine stimulation
Nutritional cofactors
Methylsulfonylmethane (MSM) Arthritides 1000-3000 mg three times per day None None
Riboflavin Migraine 400 mg per day
Lipoic acid/alpha lipoic acid/thioctic acid

  • Migraine prophylaxis

  • Diabetic neuropathy

600-1800 mg orally per day in divided doses600 mg daily intravenously

  • May worsen paresthesias when treatment first begun

  • May decrease blood glucose levels

S-adenosyl methionine (SAM-e)

  • Osteoarthritis

  • Fibromyalgia

800-1600 mg per day Rare episodes of mania and hypomania have been reported in depressed patients taking SAM-eDrug-herb interactions may occur with concurrent administration of serotonergic drugs, levodopa or monoamine oxidase inhibitors
Glucosamine sulfate, chondroitin sulfate Osteoarthritis 1500 mg glucosamine sulfate per day400-1200 mg chondroitin sulfate per day

  • Pediatric migraine

  • Muscle cramps

  • Dysmenorrhea

Children: 9 mg/kg/dayAdults: 250-600 mg per day

  • Magnesium citrate supplements can have an osmotic laxative effect at high doses

  • This effect may be seen to a lesser degree in other forms


  • Migraines

  • Headaches

  • Postoperative analgesia

1-20 mg, generally taken only at bedtime or just before a painful procedure May cause daytime grogginess and delayed recovery from anesthesia
Vitamin D

  • Osteomalacia

  • Diabetic neuropathy

  • Low back pain

  • Rheumatoid arthritis

  • Statin-induced myalgia

  • Migraine

  • Multiple sclerosis

1000-10,000 IU per day; doses of 50,000 IU are also frequently given for several weeks at a time Calcium oxalate nephrolithiasis Hypercalcemia, hyperphosphatemia, vitamin D toxicity, sarcoidosis
Coenzyme Q10 (CoQ10)

  • Migraines

  • Chronic fatigue syndrome

Pediatric: 1-3 mg/kg/dayAdults: 150 mg/day with food Antagonizes warfarin and other anticoagulants, may increase effect of hypotensives
Miscellaneous substances
Ginkgo biloba Migraines Raynaud phenomenon/disease Standardized extract: 120-240 mg per day, in divided doses

  • Ginkgo should be discontinued at least 36 hours prior to surgery

  • It may interact additively with other anticoagulantsDrug-herb interactions are possible with a number of other pharmaceuticals, including anticonvulsants, antidepressants, cyclosporine and thiazide diuretics

Centella asiatica Venous insufficiency 180 mg per day of total triterpenic fraction Caution in patients with cholestasis, celiac disease, fat malabsorption disorders, and deficiency of fat-soluble vitamins due to high saponin content of Centella
Viburnum opulus (Cramp bark), Viburnum prunifolium (Black haw) Dysmenorrhea V. opulus : Tincture: 5-10 mL (1:5) three times per dayEncapsulated or decocted crude herb: 2-4 g three times per day V. prunifolium : Tincture: 5-10 mL (1:5) three times per dayEncapsulated or decocted: 2.5-5 g three times per day

  • V. prunifolium is also used to treat hypertension; use caution in hypotensive patients

  • This herb also contains oxalates and is generally given in doses too low to warrant caution in patients with calcium oxalate nephrolithiasis

Scutellaria laterifolia (Skullcap), Scutellaria baicalensis (Huang Qin) Osteoarthritis

  • Dried herb: 1-2 g three times per day

  • Liquid extract (1:2): 0.6-1.5 mL three times per dayTincture (1:5): 1-2 mL three times per day

Not to be used for extended periods during pregnancy None
Rosa canina Osteoarthritis 4-5 g powder twice daily None currently known None currently known
Solidago chilensis (Brazilian arnica) Low back pain 10 g gel applied topically twice daily Allergy to members of the Asteraceae family

Chinese Herbal Medicine: Ancient and Modern

Chinese medicine is one of the most ancient healing systems on the planet. Based on a distinctive physiology quite unlike Western medicine, it is still in use today. Herbs play a central role in Chinese medicine, although acupuncture is more widely accepted in Western society. Unlike in Western cultures, herbs in traditional Chinese medicine are almost always given in complex formulas, as it was observed that combining herbs produces a stronger, more specific therapeutic effect, and that herbs used together mitigate some of the adverse effects they may engender as single entities. Formulation is still the most common way to prescribe Chinese herbs. Nevertheless, biochemical and pharmaceutical research techniques have been extensively applied to Chinese herbs, and now single-herb medicines or isolated constituents extracted from single herbs are used more widely. Caution is warranted with these much more recent innovations, and the traditional formulas are preferred in most cases. Many of these same arguments could be made about traditional medicine systems from around the world, such as Ayurveda and Unani-Tibb in South Asia, or Native American medicine.

Antiinflammatory Herbal Medicines

Curcuma Longa (Turmeric)

The rhizome of Curcuma longa is ground or tinctured (1:2 ratio, >45% ethanol content) to make medicine. Most supplements use curcumin, a mixture of lipophilic polyphenolic compounds including diferuloylmethane, demethoxycurcumin and bisdemethoxycurcumin found in the rhizome. It is traditionally used for pain and has been shown to modulate inflammatory cytokines including IL-1β, IL-12, IL-6, TNF-α, and IFN-γ.

  • Osteoarthritis: In the treatment of knee osteoarthritis pain, the efficacy and safety of Curcuma were found to be comparable to those of ibuprofen.

  • Rheumatoid arthritis: Curcumin inhibited proliferation of, and induced apoptosis in, the synovial fibroblasts of rheumatoid arthritis (RA) patients in vitro.

  • Dosage: 1 to 10 g powdered rhizome three to five times per day or tincture (1:1 or 1:2) 3 to 10 mL three to five times per day. 500 to 2000 mg curcumin three to five times per day.

  • Cautions/contraindications: Patients on anticoagulant therapies should not be given doses of Curcuma longa in excess of 15 g per day. Turmeric (but not curcumin extracts) contains large quantities of oxalate and should be taken with high-fiber and high-calcium foods to avoid exacerbation of kidney stones. Per German Commission E monographs, it should not be given in cases of biliary obstruction.


Bromelain is a mixture of enzymes derived from pineapple. Its effects are mainly a product of its proteolytic activity, which stimulates fibrinolysis by increasing plasmin, but bromelain also has been shown to prevent kinin production and to inhibit platelet aggregation. Because its mechanism of action is generally antiinflammatory, rather than specific to a particular disease process, bromelain is used to treat a variety of pain and inflammatory conditions. When given to treat pain, it must be administered away from food because it will act as a digestive enzyme if consumed with food.

  • Sports medicine: A study examining the effects of a mixture of proteases, including bromelain, after downhill running concluded that these enzymes improved post-workout recovery of contractile function and attenuated duration of muscle soreness compared to placebo. Another study comparing placebo to ibuprofen and to bromelain in a trial of eccentric exercise (weightlifting) found that neither ibuprofen nor bromelain improved delayed onset muscle pain (elbow flexor soreness), range of motion or concentric peak torque compared to placebo.

  • Arthritic and knee pain: Bromelain improves functionality and decreased pain in mild acute knee pain and knee osteoarthritis. In one study, efficacy of treatment with a bromelain-rutoside-trypsin product compared favorably to treatment with diclofenac. A review article found bromelain effective for treatment of knee and shoulder osteoarthritis, but reported varying degrees of patient tolerance to high doses. Adverse effects included diarrhea, flatulence, nausea, dry mouth, unspecified allergic reaction, and skin irritation.

  • Wound healing: Bromelain may be useful postsurgically to shorten healing time and to reduce levels of edema, pain, and ecchymoses.

  • Dosage: 500-2000 mg three or more times per day (potency of 2400 mcu or 3200 gelatin dissolving units (gdu) per 1000 mg) away from food.

  • Cautions/contraindications: Animal studies indicate that bromelain inhibits fibrinogen synthesis and increases fibrinolytic activity. Although bromelain has not been shown to increase risk of bleeding, this result is theoretically possible.

Omega-3 Oils

Omega-3 essential fatty acids are used by the body to form cell membranes and antiinflammatory prostaglandins, among other important molecules. Murine studies indicate that these fats produce resolvins and protectins, novel lipids with antiinflammatory properties. Although these fatty acids do not act specifically on nociceptive pathways, their administration has the well-documented effect of reducing inflammation in the body.

Fish oils are a major source of omega-3 fatty acid supplementation, especially of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are direct precursors of series three prostaglandins. Flax oil also contains a high proportion of α-linolenic acid, which is itself a precursor to DHA and EPA, but requires enzymatic conversion before having a direct antiinflammatory effect and is, therefore, less efficient for this purpose. Because of this, DHA and EPA have stronger and more direct antiinflammatory effects.

A study comparing two marine oils (seal and cod liver oils) found no difference in their efficacy, suggesting that the origin of the fatty acids is less important than their EPA/DHA content. Fatty acid source is a concern with regard to heavy metal and PCB content of the supplements, and only products that employ third-party verification of purity should be given.

  • Exercise tolerance: A study examining post-exercise pain in men who were not part of a regular training program found that administration of omega-3 fatty acids reduced pain and improved range of motion 48 hours after exercise.

  • Myocardial and skeletal muscle membranes take up omega-3 fatty acids at a higher rate than other organs. A study of fish oil administration showed that this incorporation results in decreased myocardial oxygen consumption with the same degree of performance; lower resting heart rate; and decreased episodes of arrhythmias. In skeletal muscle, fish oil administration resulted in increased insulin sensitivity and efficiency.

  • Arthritides: A Cochrane meta-analysis of patients with rheumatoid arthritis or joint pain secondary to dysmenorrhea or inflammatory bowel disease found significant reduction in patient-reported pain, NSAID consumption and number of painful joints. The authors concluded that benefit is likely for osteoarthritis patients as well, although clinical trials are still needed.

  • Dosage: 6 to 9 g fish oil providing 1.8 g EPA per day minimum. At least 3 months of treatment is usually required to see therapeutic effect.

  • Caution/contraindication: Caution: May cause bruising in some individuals. Data are varied as to whether or not omega-3 fatty acids inhibit clot formation. One study found that omega-3 acids potentiate the effects of dual antiplatelet therapy (aspirin and clopidogrel). A placebo-controlled study examining interactions between omega-3s and warfarin found that 3 to 6 g of fish oil given daily did not produce a statistically significant difference in PT-INR. Contraindication: Some sources give a contraindication for omega-3 fats presurgically because of their possible anticoagulant effects.

Angelica sinensis (Dang Gui, Tang Kui, Dong Kuai)

The root is used as medicine and the herb is tinctured, decocted, or powdered and encapsulated. In China, it is also injected locally into areas of low back and postsurgical pain with significant improvement of symptoms. Angelica is commonly used in Chinese medicine for gynecologic complaints, including dysmenorrhea. Active constituents include ligustilide, which has been demonstrated in murine studies to be antinociceptive and antiinflammatory.

  • General pain: A controlled clinical trial found that Angelica improved pain and intensity during cold pressor testing.

  • Dysmenorrhea: Aqueous and ethanol extracts of Angelica tend to stimulate the uterus, whereas the essential oil inhibits its contraction. Interestingly, studies have shown that administering the herb to a contracted uterus results in relaxation, whereas administering it while the uterus is relaxed results in contraction. In traditional Chinese medicine, decoction is the most common mode of administration, but a study in which the essential oil was given reported a 76% reduction in dysmenorrhea.

  • Dosage: 4.5 to 15 g dried root per day in divided doses.

  • Caution/contraindications: Contraindications: Should not be given during pregnancy in women with a history of miscarriage. Traditionally not used in cases of diarrhea or acute viral infection. In one study, Angelica potentiated warfarin’s anticoagulant effects, although the herb does not affect prothrombin time when given alone (and thus may have worked by inhibiting platelet aggregation). Because of these findings, it is theorized that Angelica may interact with other anticoagulants as well. In traditional Chinese medicine, it is used after the first trimester of pregnancy, although its use in pregnancy is contraindicated altogether in other sources.

Zingiber officinalis (Ginger)

The rhizome of Zingiber has been used in traditional Asian medicines, including Chinese and Ayurvedic herbalism, for millennia. Today, it is administered as encapsulated powder, in decoction, food, or tincture. Ginger is more commonly used for treatment of digestive complaints than it is for pain, but has been shown to inhibit prostaglandin and thromboxane formation in platelets and serotonin receptors in vivo. In vitro studies of human synoviocytes have demonstrated that Zingiber extract inhibits TNF-α activation and cyclooxygenase-2 expression.

  • Migraines: A product which combined Tanacetum and Zingiber demonstrated effect in aborting incipient migraine when treatment was administered in the headache’s early phases. Results were promising, although the study was of small size. No definitive studies have yet been performed, but evidence suggests that Zingiber may be effective in migraine prophylaxis.

  • Dysmenorrhea: A double-blind clinical trial found Zingiber to be as effective as ibuprofen in treating pain and reducing severity of dysmenorrhea.

  • Arthritides: Study data are mixed, with one showing reduction of symptoms of knee osteoarthritis and another crossover study showing symptomatic improvement of osteoarthritis only before crossover. Some relief of pain and swelling was reported in a retrospective case analysis of rheumatoid arthritis, osteoarthritis, and myalgia patients.

  • Dosage: 250 mg-1 g encapsulated, one to four times per day; tincture (1:3 to 1:5) 1 to 5 mL one to four times per day; eaten with food as tolerated.

  • Caution/contraindications: Caution in gastric diseases such as peptic ulceration, doses of less than 4 g per day in persons on anticoagulant therapies or with risk of hemorrhage. There is a theoretical concern that Zingiber may inhibit clotting, but relatively little data supporting that assertion. One study found that administration of moderate doses (3.6 g powdered rhizome extract per) did not alter PT-INR. Another study demonstrated that one 10 g dose of powdered rhizome resulted in decreased platelet aggregation in patients with coronary artery disease. A second study found that Zingiber counteracted the antifibrinolytic properties of fatty meals and even increased fibrinolysis. Other studies, however, including one in which subjects consumed 15 g of fresh rhizome or 40 g of cooked stem, found no antiplatelet activity in vitro.

Harpagophytum procumbens (Devil’s Claw)

This herb is native to southern Africa, and it grows in a fairly limited distribution, making it somewhat threatened in the wild. Because of this, only cultivated material should be purchased. The tuber is used therapeutically, and active constituents appear to be iridoid glycosides including harpagosides. This herb is usually administered as an aqueous or alcohol extract. Mechanism of action is unknown, but appears to be mediated via the central nervous system with possible peripheral antinociceptive effects. A rodent study found that its effects were attenuated by naloxone administration, suggesting that it acts at least in part via opioidergic pathways.

  • Low back pain: Two studies provided strong evidence that a dose of 50 mg harpagosides per aqueous administration provides short-term relief for low back pain. Another provided moderate evidence that 100 mg harpagosides per aqueous dose effectively reduces low back pain in the long term. Furthermore, 60 mg harpagosides taken daily for short-term treatment of chronic low back pain was as effective as 12.5 mg rofecoxib.

  • Dosage: Standardized extract providing 50 to 100 mg harpagosides per day. Tincture (1:2-1:5): 4 to 5 mL three times per day. Liquid extract (1:1): 3 to 4 mL three times daily.

  • Caution/contraindication: Contraindicated in hyperchlorhydria, acute peptic ulcers, and acute diarrhea. Harpagophytum may potentiate warfarin.

Boswellia serrata (Frankincense)

Boswellia acts as an antiinflammatory by its inhibition of 5-lipoxygenase, although it has no apparent effect on cyclooxygenase. Because it is a resin, it is relatively hydrophobic and must be tinctured by using a menstruum with high ethanol content. In Chinese herbal medicine, Boswellia carterii , a similar species, is an important herb for treatment of pain and healing of ulcers and is often paired with myrrh. Extracts may be standardized to 37.5% to 65% boswellic acids (considered to be the active constituents), although it may also be taken as crude herb in pill or capsule form, or, in Chinese herbal medicine, used topically or added in small amounts to decoctions of other herbs. Adverse effects may include gastrointestinal symptoms because tannins are sometimes difficult to digest.

  • Osteoarthritis: B. serrata increases joint flexion and reduces pain in knee osteoarthritis. Compared to valdecoxib, Boswellia ’s therapeutic activity had a slower onset but persisted longer (valdecoxib’s effects did not persist after cessation of therapy, whereas the Boswellia group maintained improvement up to 1 month after cessation). Boswellia administration resulted in statistically significant improvement of pain, stiffness, and ability to perform daily activities. A double-blind, placebo-controlled clinical trial for 5-loxin, a Boswellia extract enriched with 30% 3- O- acetyl-11-keto-beta-boswellic acid (AKBA) found that, administration of the drug resulted in statistically significant reduction of pain, improvement of functional ability, and reduction in levels of matrix metalloproteinase-3 in synovial fluid. Diarrhea, abdominal pain, nausea, mild fever, and weakness were reported as adverse effects.

  • Collagenous colitis: A small study demonstrated greater clinical remission rate with administration of Boswellia extract than with placebo after 6 weeks of treatment.

  • Dosage: 150 to 400 mg boswellic acid taken three times daily.

  • Caution/contraindications: Caution: may cause contact dermatitis or mild diarrhea or urticaria.

Tanacetum parthenium (Feverfew)

The leaf is typically used as medicine and is eaten fresh or taken as tea, encapsulated crude herb or tincture. It appears to act by inhibiting formation of prostaglandins in the arachidonic acid pathway, inhibiting serotonin and histamine secretion, preventing platelet aggregation, or by reducing vascular response to vasoactive amines. Parthenolide is supposedly one of the major active constituents and appears to inhibit arachidonic acid release, but studies using parthenolide alone do not yield the clinical results obtained by administration of the whole herb.

  • Migraine: Feverfew has been shown to decrease frequency and severity of migraines when used as a prophylactic, including in a double-blind, randomized, controlled trial. A study that used a high-percentage (90%) ethanol extraction did not demonstrate efficacy against migraines, suggesting that such a high proportion of ethanol does not adequately extract the constituents necessary for therapeutic effect. As a consequence, crude herb, aqueous extracts or extracts with an ethanol content below 90% are more likely to have positive clinical effect. Additionally, like many pharmaceutical treatments for migraines, patients sometimes present with rebound migraine, sleep symptoms, and anxiety after withdrawal from long-term T. parthenium use.

  • Although most studies examine Tanacetum ’s use as a migraine prophylactic, a small study demonstrated that product containing Tanacetum and Zingiber demonstrated effect in aborting incipient migraine when treatment was administered in the headache’s early phases.

  • Dosage: 25 to 225 mg per day. Tincture (1:2 or 1:3) 3 to 5 mL three times per day for prevention and up to 10 to 12 mL five times a day for acute treatment. Patients may chew one to three fresh leaves daily for migraine prophylaxis, although mouth ulcers are occasionally reported with this administration.

  • Caution/contraindications: Caution in allergy to members of the Asteraceae (Compositae) and during pregnancy because it may stimulate uterine contraction.

Centrally-Acting Herbs and Supplements

Corydalis yanhusuo

A member of the poppy family, Corydalis yanhusuo is one of traditional Chinese medicine’s chief herbs for relieving pain. The rhizome is used. Like many Chinese herbs, it is traditionally taken as an aqueous extract (i.e., decocted as tea, although it is also given as tincture [1:3 to 1:5]) or in pill or capsule form. Substitution of other species of Corydalis for C. yanhusuo is not recommended because their actions appear to differ. Its primary active constituents are alkaloids, including berberine, corydaline, and tetrahydropalmatine. Various studies have compared Corydalis extracts to morphine and findings vary, indicating that they have from 1% to 40% the analgesic effect of morphine.

  • General pain: A controlled clinical trial found that Corydalis improved pain and intensity during cold pressor testing. Besides its antinociceptive effects, Corydalis may be especially suited to generalized pain in cancer. On its own, Corydalis exhibits antimetastatic, antiproliferative, and antiangiogenic activity in vitro, the latter apparently via inhibition of the VEGF pathway. A study of the synergistic effects of Corydalis and Curcuma wen-yujin found that combining the herbs in a 3:2 ratio had stronger anticancer effects than either components used singly.

  • Dysmenorrhea: A study of corydaline found it effective in relieving dysmenorrhea in 73% of subjects.

  • Dosage: Crude herb, decocted: 4.5 to 12 g per day, divided doses. Tincture: (1:2 to 1:5) 0.25 to 1 mL three times daily.

  • Caution/contraindication: In Chinese medicine, this herb is generally contraindicated during pregnancy.

Cannabis sativa

The active constituents of Cannabis sativa (marijuana) are primarily cannabinoids, found in the greatest quantity in the flowering/fruiting tops of the plant. Many cannabinoids have been identified, the most well-known of which is tetrahydrocannabinol (THC). As an herb, Cannabis is most commonly taken by smoking or vaporizing, eating the plant, often in other foods, or via oromucosal sprays or capsules. The herb itself is illegal under United States federal law, although some states permit its prescription. Many studies performed on Cannabis have used a synthetic form of THC (most notably dronabinol [Marinol]) or other cannabinoids such as cannabidiol (CBD), although whole herb administration and plant extracts have also been studied.

Research into the mechanism of cannabinoid receptors in the body is ongoing, but suggests that they play a role in the pain-mediating effects of cannabinoids. Two major types of receptors, CB1 (found primarily in the nervous system, both centrally and peripherally) and CB2 (found in nonnervous tissues, including immune cells), have been identified.

  • Acute postsurgical pain: A dose-escalation study showed that 10 mg of Cannabis extract (with defined THC and CBD content in a 1:0.5 ratio) administered postsurgically provided rescue analgesia after opioid administration had been discontinued.

  • Neuropathic pain: Some studies of cannabinoid treatment in end-of-life pain management have also been performed, often by using dronabinol. Cannabis has also been shown to improve muscle and nerve in HIV patients and the cannabinoid CT-3 was shown to have effect on neuropathic pain in end-of-life care. Cannabinoids were also found to be effective in managing neuropathic pain in conditions such as diabetic neuropathy, brachial plexus avulsion, and multiple sclerosis (in which cannabinoids have also been seen to subjectively improve symptoms of spasticity).

  • Improved sleep: At least two studies also show increased sleep quality with Cannabis administration, which is likely to be of benefit in pain management.

  • Rheumatoid arthritis: A preliminary placebo-controlled trial found that a standardized Cannabis extract (2.7 mg THC and 2.5 mg CBD per dose) significantly reduced symptoms of pain and inhibited disease progression in rheumatoid arthritis.

  • Severe pain management: Opioids are regarded as the most effective therapy for severe pain, but adverse effects and tolerance may pose significant problems with their use. Besides the analgesic effects of Cannabis, which occur on a pathway independent of that of the opiates, it may also be used in concert with opioids to treat severe pain. Non-psychoactive doses of THC may act as opiate-sparing agents, just as THC acts synergistically with opioids and mediates effects of opioid tolerance. This may allow for reduced dosing of opiates to treat major pain and fewer adverse effects of tolerance.

  • Dosage: Further study is necessary to establish dosing guidelines.

  • Contraindications: Use of Cannabis , especially in adolescents and people at risk for mental illness, may be related to onset of psychological diseases such as psychosis or schizophrenia.

  • Cautions: Although dosage has not been well-established, a study examining the effects of smoking Cannabis on capsaicin-induced pain demonstrated hyperalgesia at high Cannabis doses, suggesting that a therapeutic window should be established. Caution in patients with hepatitis C is warranted because Cannabis smoked daily may hasten progression of hepatic fibrosis.

Hypericum perforatum (St. John’s Wort)

The aerial parts of the plant are used as medicine. Hypericum may be given internally as a tincture, decoction, or encapsulation, or used topically as a lotion. Hypericin, hyperforin, and flavonoids are thought to be the major active constituents. This herb is most commonly associated with treatment of depression but eclectic physicians used it topically as a vulnerary and internally to treat neurogenic pain, including sciatica and rheumatic pain.

Two murine studies demonstrated antinociceptive properties of H. perforatum . These properties are dose-dependent in a bell-shaped trend, i.e., therapeutic effect may only be derived from doses that are neither too low nor too high. Hypericum ’s mechanism of nociceptive action seems to be due to hypericin’s inhibition of protein kinase C and to interaction with opioid receptors, although other receptor classes may be involved. Opioid receptor involvement is supported by the finding that the herb significantly enhances the effects of concurrently administered morphine without altering serum morphine levels.

  • Otitis media: An herbal ear drop, of which Hypericum was the primary analgesic herb, was as effective as an ametocaine (tetracaine)/lidocaine ear drop in relieving pain of acute otitis media. A double-blind, randomized study of the same product found that it was more effective used alone than with amoxicillin. This latter finding supports the use of the herbal formula as a topical treatment in acute otitis media. Pain is largely self-limiting, and current American Academy of Otolaryngology-Head and Neck Surgery guidelines recommend topical treatment as first-line therapy for this condition.

  • Burning mouth syndrome: Encapsulated Hypericum reduced the number of sites of pain in stomatodynia (a condition thought to have a strong association to depressive symptoms), although the pain itself, measured by VAS scoring, was not ameliorated.

  • Neuropathy: A murine study reported that even a single dose of dried Hypericum extract significantly reduced neuropathic pain in both constriction injury and chemically-induced pain. A human study found that Hypericum had no effect on neuropathy, but as the authors of the murine noted, the human neuropathy trial likely used a dose (in that study, 2700 mcg of a product called totalhypericin) of Hypericum that exceed the window of efficacy; Hypericum ’s antinociceptive activity seems to follow a bell-shaped trend.

  • Dosage: Tincture: (1:2 to 1:5) 2 to 4 mL three or more times per day. Decoction: 2 to 4 g dried herb taken three or more times per day. Standardized extract: 300 mg three or more times daily providing 0.3% hypericin and 5% hyperforin.

  • Caution/contraindications: Hypericum decreased circulating warfarin levels in a study of healthy volunteers via its effects on cytochrome P450 enzymes, leading to lower PT-INR and increased risk of clot formation in such patients. Hypericum does not affect baseline INR, only heparin clearance. Caution: Hypericum upregulates cytochrome P450 3A4 and possibly 2C9 and P-glycoprotein. It has been shown to reduce serum levels of drugs metabolized by P450 3A4 in the gut, although study data are limited. Drugs for which an interaction has been shown include anti-HIV protease inhibitors, cyclosporine, atorvastatin, simvastatin, finasteride, digoxin, and many others. In addition, the herb may reduce the efficacy of oral contraceptives; during Hypericum administration, other modes of back-up contraception should be considered. Hypericin-containing medicines may have photosensitizing effects at high doses and in very light-skinned people, although the doses recommended generally do not cause a problem. If there is a concern about this problem, wearing sunscreen will reduce the already low risk to nearly zero.

Bryonia alba (White Bryony)

The root is usually tinctured to make medicine and has traditionally been used for pleurisy, pain, and other inflammatory conditions. Bryonia dioica (red bryony) has the same effects as B. alba and may be substituted. This herb is prescribed in low doses only and is toxic in high concentrations. Gastric distress is the most common early sign of toxicity, although cardiac toxicity may result from excessive administration.

  • Dosage: (1:10) one drop in approximately 120 mL three times daily.

  • Caution/contraindications: Contraindicated in children, pregnancy, lactation, renal failure, and hepatic failure.

Topical Herbs and Supplements

Capsicum frutescens (Cayenne)

Capsaicin is the major active constituent of the cayenne pepper, Capsicum frutescens and Capsicum annuum . It is chiefly applied topically, either in patches or in ointment form. Commercial creams or ointments are available in 0.025% and 0.075% capsaicin concentrations. Capsaicin works as a counterirritant. It stimulates small-diameter pain fibers, thereby depleting them of substance P and preventing transmission of pain signals from the peripheral to the central nervous system. In studies of treatment for peripheral neuropathy, for instance, patients experienced benefit after 4 to 6 weeks of use, although a high-dose topical patch resulted in immediate improvement in one study. Some studies concluded that capsaicin was a poor therapy but application of capsaicin was observed only for 3 or 4 weeks. Patients may experience adverse effects on initial use.

Successful treatment with capsaicin has been most commonly reported in conditions affecting topical nerves, including postherpetic neuralgia, diabetic neuropathy, arthritis, mouth pain following chemotherapy and radiation, postmastectomy pain, and trigeminal neuralgia. However, capsicum has also been used to successfully treat cluster headaches after intranasal application.

  • Dosage: Typically requires application two or three times a day or pain sensation may return.

  • Contraindications: Capsaicin causes topical irritation on initial application, but this almost always passes with frequent use. The irritation is almost never severe. To achieve a therapeutic effect, patients must often overcome an initial period of discomfort before desensitization has occurred. Avoid contact with mucous membranes if not indicated for treatment.

Urtica dioica (Stinging Nettle)

All parts of the Urtica plant are used as medicine, although only the leaves are used to treat pain. Fresh leaves are used topically for pain as a counterirritant. Urtica leaves are covered with fine hairs with a high silicon content that break when touched and release a toxin into the skin. Like apitherapy, therapeutic effect is achieved by stinging the affected area (urtication). The toxin contains several chemicals including histamine, acetylcholine, and serotonin, and provokes urticaria and C fiber discharge.

  • Joint pain: A double-blind, crossover trial of patients with chronic base-of-thumb pain due to osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis found that urtication resulted in decreased disability levels and pain symptoms.

  • Dosage: Topical: apply fresh leaf to affected area for approximately 30 seconds two or three times. Repeat as needed.

  • Caution/contraindications: Theoretically, internal use may decrease efficacy of warfarin due to nettle leaf’s substantial vitamin K content.

Symphytum officinale (Comfrey)

Herbalists have long used Symphytum root and leaf topically and internally for treatment of pain and osseous fractures. Symphytum is available in cream, ointment, and gel forms for topical use. Active constituents include rosmarinic acid, mucopolysaccharides, allantoin, and mucilage. The discovery of unsaturated pyrrolizidine alkaloids (uPA), which are potentially hepatotoxic and carcinogenic, in Symphytum has led to the recommendation that this herb be used only topically and on intact skin. uPA are absorbed only very minimally during dermal application. The herb is still used internally for short periods because studies indicate that the alkaloids cause genetic damage only in long-term use (several months or more). uPA-free extracts may be used indefinitely.

  • Back pain: Topical Symphytum (250 g herb to 100 g cream) resulted in significantly decreased levels of pain with active motion, at rest and on palpation in patients with upper and lower back pain. The effect was strongest with higher doses, and treatment was well tolerated in all patients.

  • Osteoarthritis: An ointment containing liquid extract of Symphytum root (1:2) brought about significant reduction in pain scores for knee osteoarthritis in a double-blind, placebo-controlled trial.

  • Dosage: 1-2 g cream applied topically three to five times per day.

  • Caution/contraindications: uPA-containing extracts pose a minor risk of hepatotoxicity and carcinogenicity, although these alkaloids show only minimal transdermal absorption. uPA-free extracts pose no such risk. Do not apply to large areas of broken skin.

Arnica montana

The Arnica flower is used topically for treatment of pain and is not generally taken internally (except in homeopathic form) because of its potential toxicity. It is available commercially in gels and ointments for topical use. Active constituents include sesquiterpene lactones, flavonoids, and volatile oils.

  • Bruising: A rater-blinded study of 20% topical Arnica ointment found that the ointment decreased bruise healing time more than did petrolatum jelly or 1% vitamin K/0.3% retinol mixture.

  • Osteoarthritis: A gel preparation of Arnica tincture was as effective in relieving hand osteoarthritis pain as ibuprofen.

  • Dosage: Apply topically 3 to 5 times per day.

  • Caution/contraindications: Not to be taken internally or applied to broken skin or near the mouth. Contraindicated in pregnancy in physiologic doses. Homeopathic topical preparations do not pose risk of toxicity in pregnancy.

Dimethyl Sulfoxide (DMSO)

DMSO is an organic solvent with a variety of pharmaceutical actions, including analgesic, diuretic, bacteriostatic, membrane-penetrant, antiinflammatory, vasodilatory, and cholinesterase inhibitory effects. Data about DMSO’s analgesic effects on its own are mixed. However, when DMSO is used as a carrier for other analgesics, it increases these agents’ efficacy (in one study, lidocaine, in another, diclofenac) and reduces their morbidity.

  • CRPS: DMSO is recommended for type I CRPS, in particular the warm type, concurrent with therapeutic exercise. Weaker evidence suggests that it may be of benefit for type II CRPS.

  • Dosage: Applied topically five times per day.

  • Caution/contraindications: May cause skin irritation.

Echinacea spp. (Purple Coneflower)

The aerial parts of Echinacea may be tinctured and used as a gargle. Besides its use as an antimicrobial, extracts of Echinacea can have a numbing effect and may be used to treat pharyngeal pain. An Echinacea /sage throat spray was found to be as effective and as well-tolerated as chlorhexidine/lidocaine in treatment of acute sore throats.

  • Dosage: Throat spray: Two puffs every 2 hours for duration of symptoms. Tincture of fresh root (1:2 to 1:3) 3 to 5 mL in water as a gargle (then swallow) every 2 hours for duration of symptoms.

  • Caution/contraindications: Contraindication in allergy to members of the Asteraceae (Compositae) family.

Salicylate-Containing Herbal Medicines

Salix alba (White Willow)

The bark of Salix alba is used for pain. Other Salix species, including S. daphnoides and S. purpurea , have a higher salicylate content, but S. alba is the most well-studied of the genus and of the salicylate-containing herbs in general.

  • Low back pain: A Cochrane review showed moderate evidence that a 240 mg dose of salicin relieves acute exacerbations of chronic back pain and produced the same results as 12.5 mg rofecoxib. Effect on nonspecific low back pain is dose-dependent, with the best response seen with a 240 mg dose compared to 120 mg.

  • Osteoarthritis: Salix bark extract showed benefit in relieving pain of hip and knee osteoarthritis. After 3 weeks, results were comparable to standard treatment (which was not described), and after 6 weeks, results with Salix were superior to that of the standard treatment. Mild pain complaints responded better than did those that were more severe.

  • Dosage: Standardized extract providing 120-240 mg salicin per day in divided doses. Fluid extract (1:1): 2 to 4 mL three times per day or more. Tincture (1:2): 3 to 5 mL three to five times per day.

  • Contraindications: Salicylate allergy. There is no evidence that willow causes or promotes Reye’s syndrome; indeed, the evidence that aspirin causes the disease is weak or nonexistent.

Populus tremuloides (Quaking Aspen)

This bark of this tree and leaves contain salicylate glycosides related to those found in willow. Although they have been shown to decrease inflammation in vitro, human trials are lacking.

Hypnotic Analgesic Herbs and Supplements

Valeriana officianalis (Valerian)

Although Valeriana is more commonly associated with treatment of insomnia, it has also traditionally been used for treatment of general pain and headache.

  • Dosage: Tincture (1:2 or 1:3) 3 to 5 mL three times daily with 5 to 10 mL at bedtime, 1:2 to 1:3 extract. Standardized extract: (0.5% essential oil) 500 to 1000 mg three times per day and at bedtime.

  • Cautions/contraindications: Occasionally, Valeriana may cause agitation.

Piscidia piscipula, P. erythrina (Jamaican Dogwood)

Used traditionally to treat pain, these Piscidia species are antispasmodic, hypnotic, and anodyne. The medicinal part, the root bark, is taken as a crude herb, tinctured or administered as an aqueous extract. Aqueous extract appears to be the most potent of the extractions. Active constituents primarily appear to be rotenoids and isoflavones, the latter category including piscidone, piscerythrone, and tetrahydroxy-methoxy-diisoprenyl-isoflavone (DPI).

These herbs are commonly used in medical herbalist practice, for example for migraine, dysmenorrhea, rheumatic pain, neuralgia, sciatica, and spastic pain, but few human studies have been performed to evaluate their use. Animal studies demonstrate that the fluid extract decreases the amplitude of intestinal contractions. DPI, piscidone and piscerythrone had spasmolytic effects against oxytocin-induced contractions in rat uteri.

Symptoms of toxicity include sweating, numbness, tremors, and excessive salivation.

  • Dosage: Crude root bark (dried): 2 to 4 g three times daily. Tincture: (1:3 to 1:5) 1 to 3 mL three or more times per day.

  • Caution/contraindications: Caution: Dosing simultaneously with other sedative therapies, as Piscidia may amplify these effects. Contraindication: pregnancy, bradycardia, and cardiac insufficiency.

Eschscholtzia californica (California Poppy)

The aerial parts of the plant have been used as a hypnotic anodyne traditionally. Its hypnotic effects have been confirmed in the research literature, but few comprehensive clinical studies have been performed on Eschscholtzia to examine its role in pain management. It is taken internally, most commonly as a tincture or decoction. Although a member of the Papaveraceae family, it is traditionally regarded as one of the safest and most gentle of the anodynes and may be given to children.

  • Dosage: Tincture (1:2): 3 to 5 mL three or more times per day.

  • Caution/contraindications: German Commission E monographs indicate a caution for use in pregnancy because cryptopine, a minor constituent, causes uterine stimulation in animal studies. No such activity, however, has been observed after administration of Eschscholtzia.

Nutritional Cofactors

Methylsulfonylmethane (MSM)

MSM is produced by the adrenal glands and may be obtained in the diet from some fruits and vegetables.

  • Arthritides: MSM shows weak pain-relieving effect on its own but is more frequently given in conjunction with glucosamine with or without chondroitin. Animal studies showed that it decreased joint degeneration. Thus far, human studies showed modest effects on pain and swelling, but no effect on stiffness.

  • Dosage: 1000 to 3000 mg three times per day.

  • Caution/contraindications: None currently noted.


This B vitamin serves a variety of metabolic roles. With regard to pain control, its mechanism is similar to that of coQ10 in that it facilitates mitochondrial energy metabolism.

  • Migraine: High-dose riboflavin (400 mg per day) reduced frequency of attacks and number of days of migraine duration.

  • Dosage: 400 mg per day.

  • Caution/contraindications: None.

Lipoic Acid/Alpha Lipoic Acid/Thioctic Acid

Lipoic acid is a disulfide produced in the body. It is a small, easily absorbed molecule and is a potent antioxidant that increases the activity of catalase and superoxide dismutase in peripheral nerves, is neurogenerative and normalizes endoneural blood flow. Because it is both lipophilic and hydrophilic, it addresses both fat- and water-soluble free radical species. It is administered orally and intravenously. Coadministration of a B-complex supplement is recommended because lipoic acid may deplete these vitamins.

  • Migraine prophylaxis: Thought to have an effect similar to riboflavin and coQ10, thioctic acid showed within-group improvement in headache days, frequency, and severity of migraines in one study. Research is ongoing, and anecdotal reports are favorable.

  • Diabetic neuropathy: A critical review of several clinical trials of varying sizes found that intravenous lipoic acid significantly improved major symptoms of diabetic polyneuropathy, including that of the cranial nerves; lower limb motor and sensory nerve conduction; and deficits in nervous function and cardiac autonomic neuropathy. Furthermore, it reversed some of the vascular changes of diabetes, including elevated NF-κB, albuminuria, and elevated thrombomodulin. The analysis did not reveal any major concerns about safety. A long-term study (NATHAN I) is being conducted to further assess the role of lipoic acid in treatment of diabetic polyneuropathy.

  • Dosage: 600 to 1800 mg orally per day in divided doses; 600 mg daily intravenously.

  • Caution/contraindications: May worsen paresthesias when treatment is first begun. May decrease blood glucose levels.

S -adenosyl methionine (SAM-e)

SAM-e is the stable salt form of S-adenosyl methionine, a methyl donor produced from methionine and adenosine triphosphate in the liver. It is commonly used to treat depression, a condition in which CSF SAM-e levels tend to be low, compared to nondepressed individuals. SAM-e increases turnover of serotonin and may increase levels of dopamine and norepinephrine.

  • Osteoarthritis: SAM-e controlled osteoarthritic pain as effectively as celecoxib after 2 months of use in a study comparing the two, although celecoxib controlled pain much better in the first month.

  • Fibromyalgia: A double-blind, placebo-controlled Danish study found that 800 mg of SAM-e administered orally improved fatigue, disease activity, morning stiffness, mood, and pain experienced during the study’s final week.

  • Dosage: 800 to 1600 mg per day in divided dose.

  • Caution/contraindications: Rare episodes of mania and hypomania have been reported in depressed patients taking SAM-e. Drug-herb interactions may occur with concurrent administration of serotonergic drugs, levodopa, or monoamine oxidase inhibitors.

Glucosamine Sulfate and Chondroitin Sulfate

Although they are not anodynes in the same sense as other remedies listed here, glucosamine sulfate and chondroitin sulfate are useful in the treatment of osteoarthritis pain because of their effect on joint structure. Glucosamine is a substrate for the glycosaminoglycans that comprise hyaluronic acid, a chief component of joint tissue.

Chondroitin plays a number of roles in connective tissue synthesis. It is itself a glycosaminoglycan and, when hydrated, it creates osmotic pressure that increases the compressive resistance of synovial cartilage. It also stimulates the production of collagen and proteoglycan and inhibits enzymatic destruction of the synovium.

  • Osteoarthritis: Numerous studies have been performed to evaluate the efficacy of glucosamine and chondroitin administration for osteoarthritis treatment with mixed results, although this may be due to combining different forms of the agents, or to some studies’ use of less effective forms of glucosamine and/or chondroitin or products with poor standardization. Industry bias may also account for some of the discrepancy between studies, although it should also be noted that many of the studies not funded by industry sources examined glucosamine hydrochloride. According to a meta-analysis, glucosamine sulfate used alone relieved pain due to osteoarthritis and prevented disease progression. Glucosamine hydrochloride, although cheaper, is not effective for osteoarthritis. Conclusions derived from studies of one form cannot be extrapolated to apply to the other form, even though data for glucosamine sulfate are mixed.

  • Chondroitin treatment reduced pain, swelling, and effusion, and maintained or improved joint space and serum osteocalcin levels. Glucosamine sulfate and chondroitin sulfate taken together decreased pain and joint effusion in moderate-to-severe arthritis pain, but results were inconsistent between studies.

  • Dosage: 1500 mg glucosamine sulfate per day. 400 to 1200 mg chondroitin sulfate per day.

  • Caution/contraindication: Contraindication for glucosamine: shellfish or iodine allergy. Glucosamine may increase PT-INR when given with warfarin. Chondroitin may also increase the effects of anticoagulant therapies. Because of its structural similarities to heparin, some sources recommend that it be contraindicated in pregnancy.


Used clinically for a wide range of conditions, magnesium is given in a variety of forms, including magnesium citrate, glycinate, and oxide. Food sources include green leafy vegetables, whole grains, nuts, and seeds.

  • Pediatric migraine: An intention-to-treat analysis of magnesium oxide administration found a significant reduction in migraine days compared to placebo.

  • Dysmenorrhea: Magnesium likely inhibits prostaglandins and was found to be superior to placebo in the treatment of dysmenorrhea.

  • Dosage of elemental magnesium: Children: 9 mg/kg/day; Adults: 250 to 600 mg per day in divided doses, to bowel tolerance.

  • Caution/contraindications: Magnesium citrate supplements can have an osmotic laxative effect at high doses. This effect may be seen to a lesser degree in other forms.

Hormonal Analgesics


Research on melatonin has examined the hormone’s influence on nonendocrine tissues and has elucidated the mechanism by which it might influence pain. It is present throughout the central nervous system, and has been shown to treat acute, inflammatory, and neuropathic pain symptoms.

  • Migraines/headaches: Melatonin levels are frequently low in migraineurs and cluster headache patients. Many of the symptoms of migraine prodrome seem to originate in the hypothalamus, which exerts regulatory input over the pineal gland and its melatonin production. Melatonin is also present in significant amounts in the trigeminal ganglion, which may also be involved in migraine initiation. It is unknown if melatonin plays a direct role in headache pathogenesis, or if decreased melatonin simply is another sign of hypothalamic dysfunction, but melatonin treatment has been shown to ameliorate headache symptoms in some individuals, especially those with clear circadian dysregulation (i.e., delayed sleep phase syndrome).

  • Postoperative analgesia: A randomized, placebo-controlled study found that patients undergoing elective prostatectomy who were given 6 mg melatonin the night before and 1 hour before surgery had less pain, used less intraoperative fentanyl, required less tramadol, and had better postoperative sleep than the placebo group. The treatment group, however, had greater extubation time and took longer to recover from anesthesia.

  • Dosage: 1 to 20 mg, generally taken only at bedtime or just before a painful procedure.

  • Caution/contraindications: May cause daytime grogginess and delayed recovery from anesthesia.

Vitamin D

Although vitamin D is a nonessential vitamin, recent research has demonstrated epidemic deficiency of this vitamin in the general population, especially in the elderly, institutionalized populations, those who live in northern latitudes, with limited sun exposure or who have dark skin. It is available in pill, capsule, powder, and liquid forms. Vitamin D deficiency has been linked with a variety of painful disease states, including bone loss and attendant fractures, pelvic floor disorders, systemic lupus erythematosus, tuberculosis, certain cancers, and inflammatory bowel diseases. A 2008 review article, however, found that studies demonstrating a link between hypovitaminosis D and chronic pain were largely of poor quality and that too few randomized controlled trials had been performed. Although vitamin D2 (ergocalciferol) and D3 (cholecalciferol) are both available commercially, the D3 form of the vitamin is more potent and has longer-lasting effects.

Vitamin D intoxication is reported rarely, and published cases all involve persons who consumed at least 40,000 IU per day long-term. Evidence suggests that the currently accepted No Adverse Effect Limit of 2000 IU per day is probably too low “by at least five fold.” No adverse effects are seen in individuals who are not hypersensitive when serum levels of 25(OH)D are less than 140 nmol/L (56 ng/mL), which is attained in healthy people by consuming 10,000 IU per day long term. Another study whose subjects’ serum concentrations reached 400 nmol/L reported no observable hypercalcemia, hypercalciuria or adverse effects. Although dosages of 10,000 IU per day may be taken long-term without major problems, very large single doses of vitamin D are not recommended. A study in which a massive single dose of vitamin D (500,000 IU) was given to women older than age 70 with normal baseline serum levels demonstrated that such high doses increased the risk of fracture and falling.

  • Osteomalacia: Supplemental vitamin D is crucial to treatment of osteomalacia, as hypovitaminosis D is a key component of the disease’s pathogenesis. Pain may worsen before improvement is seen following treatment.

  • Diabetic neuropathy: Type 2 diabetics are commonly deficient in vitamin D. Repletion of vitamin D levels in these patients resulted in significant reduction of neuropathic pain. Pain scores were negatively correlated with serum 25(OH)D levels, although no correlation between pain and serum iPTH levels was observed.

  • Low back pain: A study of 360 Saudi Arabian men and women with low back pain of no obvious etiology found that 83% had deficient levels of vitamin D. Another reported a similar finding among Egyptian women. However, treatment was not performed as part of either study.

  • Rheumatoid arthritis: A vitamin D receptor has been identified on human immune cells. In its capacity as a hormone, vitamin D seems to downregulate autoimmunity caused by excessive Th-1 activity. Serum 25(OH)D levels are inversely correlated with disease activity in rheumatoid arthritis. People with autoimmune diseases may have a higher vitamin D requirement to maintain optimum serum levels.

  • Myalgia in statin-treated patients: 92% of statin-treated patients with concurrent myalgia/myositis and hypovitaminosis D saw resolution of myalgia/myositis after 12 weeks of 50,000 IU vitamin D per week (the form of the vitamin given was not identified).

  • Migraine: Case studies report successful treatment of menstrual and postmenopausal migraine with vitamin D and calcium, although no large-scale studies have so far been performed.

  • Multiple sclerosis: The Nurses’ Health Study demonstrated that women whose serum vitamin D levels were in the highest quintile were 40% less likely to develop multiple sclerosis.

  • Dosage: Vitamin D3, or cholecalciferol, is the preferred form. Recommended daily allowances are 200 to 600 IU per day, depending on age, with a maximum safe level of 2000 IU per day, but evidence suggests that doses necessary to treat deficiency and even to maintain normal levels are much higher (5,000 to 20,000 IU per day). Due to interactions between these vitamins in vivo, it is recommended to give high-dose vitamin D with small amounts of vitamins A and K.

  • Therapeutic dose: 1000 to 10,000 IU per day long term. Weekly doses of 50,000 IU are also given, usually for shorter durations (e.g., 4 to 6 weeks).

  • Caution/contraindications: Contraindications: Hypercalcemia, hyperphosphatemia, vitamin D toxicity, and sarcoidosis. Caution in calcium oxalate nephrolithiasis.

Coenzyme Q10 (CoQ10)

Coenzyme Q10 acts as a mitochondrial electron-transport chain cofactor in the reactions that produce ATP. It scavenges free radicals and is a component of the Krebs cycle enzyme succinate dehydrogenase-coQ10. Its alternate name, ubiquinone, reflects its omnipresence throughout the body. Despite the fact that coQ10 is synthesized innately, it is commonly deficient in the general population. Its production decreases with age and it is depleted by many pharmaceuticals, including beta blockers, antipsychotics, some statins, metformin, sulfonylureas, and some tricyclic antidepressants. Animal studies demonstrate that its antinociceptive effects may be a consequence of its downregulation of nitric oxide. Two forms are available commercially—ubiquinone and ubiquinol (ubiquinone’s reduced form). Ubiquinol is more commonly given clinically.

  • Migraines: CoQ10 deficiency may be a predisposing factor in the incidence of migraine headaches. Prophylactic coQ10 supplementation in adult migraineurs and repletion of coQ10 in pediatric migraineurs with low serum levels decreased migraine frequency.

  • Chronic Fatigue Syndrome: Although the role of oxidative stress and mitochondrial dysfunction in chronic fatigue syndrome is controversial, coQ10 levels were found to be low in such patients. Supplementation may improve symptoms of chronic fatigue syndrome.

  • Dosage: Pediatric: 1 to 3 mg/kg/day. Adults: 150 mg/day with food.

  • Caution/contraindications: Antagonizes warfarin and other anticoagulants, may increase effect of hypotensives.

Miscellaneous Agents

Ginkgo biloba (Ginkgo)

Ginkgo is most commonly prescribed for vascular disorders, including those pertaining to perfusion of the central nervous system. The leaves are used in Western herbalism, and the seed kernel is used in traditional Chinese herbal medicine. Active constituents include ginkgolides A, B, C, and J (all diterpene lactones), bilobalide (a sesquiterpene lactone), and flavonol glycosides. Ginkgo is available as tincture, capsules, tablets, decoction, and standardized extract—usually in solid form. The standardized extract is the most well-researched preparation and contains 24% to 32% flavonoids and 6% to 12% terpenoids. The standardized extract form is the most recommended by some sources because proportions of active constituents may vary widely between different samples of crude herb.

  • Migraine: A preliminary trial found that an extract containing ginkgolide B reduced frequency and duration of migraine attacks in adults. Another preliminary trial found that Ginkgolide B given prophylactically with coQ10, vitamin B 2 and magnesium reduced frequency and need for pain medication in a small group of pediatric migraineurs.

  • Raynaud’s phenomenon/disease: A standardized extract of Ginkgo was effective in reducing number of attacks in patients with Raynaud’s phenomenon compared to placebo. Anecdotal evidence also suggests effectiveness in Raynaud’s disease of the nipple during lactation.

  • Intermittent claudication: A 2000 meta-analysis found that Ginkgo extract was slightly more effective than placebo in increasing walking distance, although not as effective as vasodilators. A more recent Cochrane review, however, found that Ginkgo offered no benefit in treatment of this condition.

  • Dosage: Standardized extract: 120 to 240 mg per day, in divided doses.

  • Caution/contraindications: Ginkgo should be discontinued at least 36 hours prior to surgery. It may interact additively with other anticoagulants. Drug-herb interactions are possible with a number of other pharmaceuticals, including anticonvulsants, antidepressants, cyclosporine, and thiazide diuretics.

Centella asiatica (Gotu Kola)

Centella has been used in traditional herbal medicines across Asia. The whole plant is used, and dosage forms include encapsulation of the crude herb, decoction, and tinctures. Active constituents include triterpenoid saponins and notable amounts of asiaticoside, madecassoside and madecassic acid. A murine study demonstrated that the crude herb possesses antiinflammatory and antinociceptive properties. Its effects were likely mediated by the central and peripheral nervous systems and its mechanism of action may involve opioid receptors.

  • Venous insufficiency: Centella has been used traditionally for its circulatory effects. A triterpene fraction of Centella given to patients with venous hypertension decreased symptoms of edema, pain, fatigue, and restless limb more effectively than placebo. Capillary filtration rate was also decreased, as was ankle circumference, in patients receiving the Centella extract.

  • Dosage: 180 mg per day of total triterpenic fraction. Tincture or glycerite of fresh plant (1:2 to 1:3) 3 to 5 mL three or more times per day. Topical cream 1-2 g two or more times per day.

  • Caution/contraindications: Caution in patients with cholestasis, celiac disease, fat malabsorption disorders, and deficiency of fat-soluble vitamins due to Centella ’s high saponin content.

Viburnum opulus (Cramp Bark), Viburnum prunifolium (Black Haw)

The bark of both species is used medicinally and may be decocted, tinctured, or encapsulated as crude herb. Viburnum opulus contains hydroquinones, coumarins, and tannins, whereas Viburnum prunifolium ’s primary constituents include coumarins, biflavones, and phenolic acids.

  • Dysmenorrhea: Both Viburnum species treat dysmenorrhea, although classically, V. opulus is used for pain radiating into the thighs and V. prunifolium is specific for severe low back pain with a feeling of bearing down in the pelvis. Animal studies demonstrate that both herbs have relaxant effects on the uterus, and this effect has also been described in humans in studies of V. prunifolium.

  • Dosage: V. opulus : Tincture: 5 to 10 mL (1:5) three times per day. Encapsulated or decocted crude herb: 2 to 4 g three times per day. V. prunifolium : Tincture: (1:3 to 1:5) 5 to 10 mL (1:5) three times per day. Encapsulated or decocted: 2.5 to 5 g three times per day.

  • Cautions/contraindications: Caution: V. prunifolium is also used to treat hypertension; use caution in hypotensive patients. This herb also contains oxalates but is generally given in doses far too low to warrant caution in patients with calcium oxalate nephrolithiasis.

Scutellaria laterifolia (Skullcap)

Scutellaria baicalensis (Huang qin)

This herb has been part of traditional Chinese materia medica for millennia and is used to treat pain and inflammatory conditions. Its active constituents include baicalin, a flavonoid, the herb’s most studied component.

  • Osteoarthritis: A short-term, randomized, double-blind study found that a supplement (flavocoxid, given 500 mg twice per day) combining baicalin and catechin (a flavan derived from Acacia catechu ) was as effective as naproxen in treating osteoarthritic knee pain. The mechanism of action is likely inhibition of COX-2, LOX-5 and NF-κB.

  • Dosage: Dried herb: 1 to 2 g three times per day. Liquid extract (1:2): 0.6 to 1.5 mL three times per day. Tincture (1:5): 1 to 2 mL three times per day.

  • Caution/contraindications: Not to be used for extended periods during pregnancy.

Rosa canina

The fruit is used medicinally and is taken internally as a decoction, alcohol extract, powder, or encapsulated. Rosa fruits generally contain high concentrations of vitamin C, although their antioxidant properties result from other components as well.

  • Osteoarthritis: A clinical trial of a powder made from Rosa canina was found to reduce osteoarthritic pain compared to placebo. A meta-analysis found Rosa powder to be twice as likely as placebo to reduce pain.

  • Dosage: 4 to 5 g powder twice daily.

  • Caution/contraindications: None currently known.

Solidago chilensis (Brazilian Arnica)

The leaves and flowers of Solidago have long been used as medicine by indigenous Brazilians. Active constituents include flavonoids, carotenes, and diterpenoids. Mouse studies demonstrate that the rhizome also possesses potent antiinflammatory activity.

  • Low back pain: In a small, placebo-controlled study, Solidago improved lumbar flexibility and reduced pain when applied topically in gel form. The majority of the subjects experienced absence of pain with treatment.

  • Dosage: 10 g gel applied topically twice daily.

  • Caution/contraindications: Allergy to members of the Asteraceae family.

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Apr 13, 2019 | Posted by in PHYSICAL MEDICINE & REHABILITATION | Comments Off on Herbal and Nutritional Supplements for Painful Conditions

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