Pharmacologic Treatments

Pharmacologic Treatments

Reena Sarah John

Yashar Eshraghi

Maged Guirguis


Foot and ankle pain are very disabling and very common among the chronic pain population. The pain can become so severe and debilitating that it compromises a patient’s overall quality of life. The worldwide prevalence already standing at 23.9% is projected to rise with the rise in obese patients and the growing elderly population.1 While lifestyle changes and preventative health strategies play a significant role, research shows that pharmacological management rates of foot/ankle pain were high and substantially exceeded nonpharmacological management.2 With proper management, those with foot osteoarthritis (OA) are able to reduce and manage their pain and in effect resume their daily activities and remain active. However, there is very little research on management strategies for foot and ankle pain.1 Surgery should be reserved for patients with moderate to severe disease due to high rates of complications and possible restriction in ankle range of motion (ROM). Early stages of the ankle OA and milder cases should be treated with more conservative, nonsurgical methods, such as pharmacological agents.3,4 The goal of pharmacological targeted therapy is to avoid invasive treatment modalities.


Foot and ankle pain is an unpleasant and uncomfortable experience following perceived damage to any tissue distal to the tibia or fibula; including bones, joints, ligaments, muscles, tendons, apophyses, retinacula, fascia, bursae, nerves, skin, nails, and vascular structure.5,6 The etiology of foot pain is multifactorial and can be associated with direct trauma, musculoskeletal overload, nerve involvement or neuropathy, loss of blood flow due to atherosclerosis, and infection such as diabetic ulcers.6 Foot and ankle pain may also be related to the presence of health conditions (eg, diabetes, gout, rheumatoid arthritis [RA], OA) or involve specific body structures (eg, plantar fasciitis, Morton neuroma, Hammertoe).


The 2 categories of foot and ankle pain are physiological and pathological foot and ankle pain. Physiological pain is characterized by an acute response to injury in healthy, properly functioning nervous systems, both peripherally and centrally. It relies on a feedback system that is in place to identify and warn the body of a harmful stimuli and remove that stimuli hopefully prior to inflicting immense tissue damage. The cascade of events with the nervous system produces the feeling of pain which is referred to as nociceptive pain.6 Pathological pain is experienced following nociceptive pathology; however, it involves dysfunction in the peripheral or central nervous systems or both. Pathological pain includes inflammatory pain, neuropathic pain, and chronic pain.


  • Trauma—fractures, sprains, tendon injury

  • Injury or overuse leading to inflammation (can involve bony structures, ligaments, tendons, and musculature)—eg, plantar fasciitis

  • Disease causing breakdown of bones and joints—OA

  • Nerve injury or peripheral neuropathy

  • Joint inflammation or bursitis

  • Structural causes—eg, bone spurs, flat feet, hammertoe, or mallet toe

  • Infection—eg, osteomyelitis, septic arthritis, plantar warts

  • Underlying disease—eg, diabetes (peripheral neuropathy, psoriatic arthritis, RA), gout

  • Malignancy—tumors


The primary aim of treatment is to alleviate pain, restore alignment, ROM in order to allow the patient to return their baseline or desired level of activity. The most important initial step is to determine that underlying cause of the foot and ankle pain. If disease or infection is the underlying cause, treatment of the underlying disease should be the initial goal. By targeting the disease process, pain can be significantly diminished. The most frequently used treatment modalities begin with conservative, nonpharmacological therapies such as rest and redistribution of load, orthoses and supportive footwear, and physical therapy and stretching.7 Although there are no clinical guidelines for the management of foot or ankle OA, it is reasonable to suggest that recommendations pertaining to the management of OA at other sites may be appropriately applied to the foot and ankle. The National Institute for Health and Care Excellence (NICE) guidelines for peripheral joint OA, developed largely from hip and knee OA trials, advise that core management strategies should include (1) advice and education regarding the disease and its prognosis, (2) strengthening and aerobic exercise, and (3) weight loss.1


Nonsteroidal Anti-inflammatory Drugs

Salicylates, Acetaminophen, and Acetic Acid Derivatives

  • Salicylates—aspirin

  • Para-aminophenol derivatives—acetaminophen

  • Acetic acid derivatives—indomethacin, sulindac, etodolac, tolmetin, ketorolac, diclofenac, nabumetone

  • Propionic acid derivatives—ibuprofen, naproxen (may provide cardioprotection), fenoprofen

  • Enolic acid derivatives—meloxicam, piroxicam

  • Diaryl heterocyclic NSAIDs (COX-2 selective)—celecoxib

Paracetamol/Acetaminophen and Topical NSAIDs

Paracetamol/acetaminophen or topical NSAIDs are generally recommended following first-line strategies. Topical NSAIDs are both safe and effective and should be considered as an adjunct to nonpharmacological strategies. There are no clinical trials on the use of topical NSAIDs for the treatment of foot/ankle OA. The most recent systematic review and network meta-analysis of 36 RCTs in predominantly hip and knee OA found that topical NSAIDs were superior to placebo for OA-related pain relief, and significantly improved physical function. Diclofenac patches, followed by ibuprofen cream, were found to be the most effective for pain.7,8 For patient suffering from neuropathic pain, topical forms of both capsaicin and lidocaine have been shown to be useful. Application of topical capsaicin can also be considered as adjunct to nonpharmacological treatments. Use of capsaicin in conjunction with nonpharmacological modalities clinically has shown significant improvements in pain that were not inferior nor superior to topical NSAIDs.9,10


When paracetamol/acetaminophen and/or topical NSAIDs or capsaicin are ineffective
for managing the symptoms of foot or ankle OA, clinicians should consider prescribing oral NSAIDs, including COX-2 inhibitors.9 NSAIDs are effective for the treatment of low to moderate inflammatory pain. They are often used prior to opioids due to their lack of detrimental adverse effects associated with opioids such as, respiratory depression, tolerance, and euphoria leading to addiction and physical dependence. That being said, the maximal efficacy for NSAIDs has been found to be less than opioids. Opioids formulations are often paired with NSAIDs to reduce the overall dose for opioids thereby reducing the likelihood of adverse effects while providing adequate pain control.

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Sep 8, 2022 | Posted by in ORTHOPEDIC | Comments Off on Pharmacologic Treatments

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