Most studies have utilised measures of quantitative sensory testing to provide an understanding of nociceptive processes. Both positive and negative sensory responses have been found to various stimuli, including hyperalgesia, allodynia as well as hypoaesthetic changes (Chien, Eliav, & Sterling, 2009; Sterling, Jull, Vicenzino, & Kenardy, 2003). Most sensory changes are widespread in nature, meaning that they are found not only over the injured area (cervical spine) but also in areas remote to the injured site, including both upper and lower limbs. These widespread sensory disturbances infer the presence of disturbed central nervous system processing which may be either facilitatory (sensitised) processes or a loss of inhibitory processes (Curatolo & Sterling, 2011). In the case of chronic WAD, two recent systematic reviews concluded that there is strong evidence of central hyperexcitability in chronic WAD (Stone et al., 2013; Van Oosterwijck, Nijs, Meeus, & Paul, 2013). These changes are not unique to WAD, but have been consistently demonstrated across many conditions including other musculoskeletal conditions such as arthritis (Bajaj, Bajaj, Graven-Nielsen, & Arendt-Nielsen, 2001), tennis elbow (Coombes, Bisset, & Vicenzino, 2012), temporomandibular joint pain (Ayesh, Jensen, & Svensson, 2007), cervical radiculopathy (Chien, Eliav, & Sterling, 2008) as well as in chronic post-surgical pain (Gottrup, Andersen, Arendt-Nielsen, & Jensen, 2000). However, there does appear to be some differences in sensory presentation among various musculoskeletal conditions. For example, cold hyperalgesia found in patients with chronic WAD, reporting moderate/severe pain and disability, seems to be greater than that observed in patients with tennis elbow and low back pain (Coombes et al., 2012; Lewis, Souvlis, & Sterling, 2010; Sterling, Jull, Vicenzino, et al., 2003), although a direct within-study comparison is yet to be undertaken. Another example is that neck pain of non-traumatic origin does not seem to display such overt sensory changes, with hyperalgesia confined to the cervical spine and little evidence of spread to distal areas (Chien, Eliav, & Sterling, 2010; Elliott et al., 2008). Taken together, these findings suggest that different nociceptive processing mechanisms likely underlie various musculoskeletal conditions, and this has implications for management where different strategies may be required depending upon the patient’s presentation, as opposed to the diagnosed condition per se.

In comparison to other musculoskeletal conditions, there has been greater research of the transition from acute to chronic WAD, most probably due to the defined onset of symptoms by a specific event. In prospective cohort studies, it has emerged that sensory disturbances are also associated with the transition from acute to chronic pain after whiplash injury. The presence of generalised hyperalgesia to a variety of stimuli, including pressure, cold and heat, has been shown to occur predominantly in individuals with acute WAD, higher pain and disability (Sterling, Jull, Vicenzino, & Kenardy, 2004) and subsequent poor recovery (Sterling, Jull, Vicenzino, Kenardy, & Darnell, 2005). Importantly, some of the sensory changes demonstrate a capacity to predict individuals at risk of poor recovery. As outlined earlier, the early presence of cold hyperalgesia is emerging as a consistent prognostic factor (Goldsmith et al., 2012). Initial studies demonstrated that, in addition to initial moderate pain, decreased neck movement, older age and PTSD symptoms, cold hyperalgesia predicted higher levels of pain and disability at both 6 months and 2–3 years post-injury (Sterling et al., 2005, 2006). Decreased cold pain tolerance, measured using the cold pressor test, has also shown predictive capacity (Kasch et al., 2005).

Of course, the sensory responses measured require a cognitive response from the person being tested, either to report pain threshold or tolerance, and thus it remains a self-report measure (and, as such, may be influenced by many other factors). Nevertheless, there is evidence of spinal cord hyperexcitability in WAD via measurement of the nociceptive flexion response. This test measures reflex muscle activity in the hamstrings following electrical stimulation over the sural nerve at the ankle, and it reflects spinal cord processes (France, Rhudy, & McGlone, 2009). Lower thresholds for reflex elicitation have been demonstrated in both acute and chronic WAD (Banic et al., 2004; Sterling, 2010). As this test does not require a cognitive response from the participant, it could be deemed a more ‘objective’ measure of central hyperexcitability, although it should be noted that descending processes (e.g. anxiety) may influence the test outcome (Banic et al., 2004).

In summary, current evidence suggests that some central nervous system pain processes are augmented from soon after injury in those individuals who do not recover following whiplash injury. The reasons as to why this group manifests more profound changes in pain processes are not clear, but there are numerous possibilities including, but not limited to, the nature, extent and duration of the original injury providing peripheral nociceptive input to the central nervous system; stress-related responses; psychological augmentation; poorer health before the injury; or a genetic predisposition. Irrespective of the cause of the changes, the data indicate that consideration of these processes in the early management of WAD will be required.

Movement and motor-related disturbances have been well investigated in both acute and chronic WAD. Loss of neck range of movement is one of the cardinal signs of WAD, which is included in the current Quebec Task Force classification system of the injury (Spitzer et al., 1995). Numerous studies have also documented its presence (Dall’Alba, Sterling, Trealeven, Edwards, & Jull, 2001; Kasch et al., 2008; Sterling, Jull, Vizenzino, Kenardy, & Darnell, 2003). While the measurement of neck movement is a staple of the clinical examination, its capacity to predict later outcome is equivocal (Walton et al., 2009). Neuromuscular control deficits have also been found to be present in patients with WAD. Neck muscle strength is decreased around all axes of motion (Lindstrom, Schomacher, Farina, Rechter, & Falla, 2011), and these changes are also accompanied by alterations in muscle strategies. The presence of neck pain is associated with alterations in task-related modulation of neck muscle activity so that motor control of the cervical spine is achieved by alternative, presumably less efficient, combinations of muscle synergistic activities. For example, altered performance on a task of upper-cervical flexion performed in the supine position is present in whiplash (Jull, 2000; Sterling, Jull, Vizenzino, et al., 2003), as well as in neck pain of non-traumatic origin (Falla, Jull, & Hodges, 2004) and cervicogenic headache (Jull et al., 2002). In this test, individuals with neck pain perform the movement of upper-cervical flexion with much greater activity in the superficial neck muscles than when performed by individuals without neck pain, and these changes are proposed to represent disturbed neuromuscular control (Falla et al., 2004). Altered patterns of muscle recruitment are not unique to whiplash, and similar changes have also been observed in neck pain of non-traumatic or insidious onset (idiopathic neck pain) (Jull, Kristjansson, & Dall’Alba, 2004; Nederhand, Hermens, Ijzerman, Turk, & Zilvold, 2002; Woodhouse & Vasseljen, 2008). These findings suggest that the ‘driver’ of such motor changes may be more due to the nociceptive input rather than the injury itself.

Structural morphological changes to muscles have also been found. Elliott et al. (2006, 2010) demonstrated the presence of fatty infiltrate in both deep and superficial cervical muscles of individuals with chronic WAD, compared to an asymptomatic control group. In contrast to neuromuscular control deficits outlined above, preliminary data indicate that similar morphological changes are not apparent in individuals with chronic idiopathic neck pain (Elliott et al., 2008). In a later cohort study, it was found that the fatty muscle infiltrate seems to develop at a time point between 1 and 3 months post-injury and that greater fatty deposits are present in those people reporting higher levels of pain and disability and who show poorer recovery at 6 months (Elliott et al., 2011). The processes that lead to the development of the muscle changes are yet to be elucidated, with possible options including muscle changes due to disuse, possible neural injury or even inflammatory processes (Elliott et al., 2011). While these scenarios require investigation, preliminary analyses indicate a relationship between stress-related symptoms and the fatty infiltrate, suggesting that stress-related responses may be at play in influencing motor and muscle function (Elliott et al., 2011). This proposal also requires further research, but data supporting a detrimental role of stress responses on tissue healing has been found elsewhere (Walburn, Vedhara, Hankins, Rixon, & Weinman, 2009).

Dysfunction of sensorimotor control is also a feature of both acute and chronic WAD. Greater joint repositioning errors have been found in patients with chronic WAD and also in those within weeks of their injury and with moderate/severe pain and disability (Sterling, Jull, Vizenzino, et al., 2003; Treleaven, Jull, & Sterling, 2003). Loss of balance and disturbed neck-influenced eye movement control are present in patients with chronic WAD (Treleaven, Jull, & Low choy, 2005; Treleaven, Jull, & LowChoy, 2005), but their presence in the acute stage of the injury are yet to be determined. It is important to note that sensorimotor disturbances seem to be greater in patients who also report dizziness in association with their neck pain (Treleaven, Jull, & LowChoy, 2005; Treleaven et al., 2003). It should also be noted that the majority of the documented movement and motor disturbances are not unique to whiplash-related neck pain, but are also found to be present in individuals with non-traumatic neck pain of insidious onset (Jull et al., 2004; Treleaven, 2008). Thus, it could be extrapolated that they are not involved in the initiation and maintenance of whiplash-related pain and disability, but rather are sequelae of as yet unexplained nociceptive processes. This is not to say that management approaches directed at improving motor dysfunction should not be provided to patients with whiplash. Rather, the identification of motor deficits alone may not equip the clinician with useful information to either gauge prognosis or potential responsiveness to physical interventions.

In contrast to many other musculoskeletal conditions that have a more insidious onset, whiplash is precipitated by a traumatic event, namely the motor vehicle crash. It has now been consistently shown that many whiplash-injured individuals report symptoms of PTSD (Buitenhuis, DeJong, Jaspers, & Groothoff, 2006; Sterling & Kenardy, 2006; Sullivan et al., 2009), and it is likely that physiological stress-system responses may also contribute to later poor health outcomes. In light of this, models have been proposed to theoretically link stress-system responses (e.g. sympathetic nervous system activity) to recovery outcomes, as well as to other clinical features of WAD, including hyperalgesia, muscle and motor disturbances (McLean, Clauw, Abelson, & Liberzon, 2005; Passatore & Roatta, 2006). Indeed, there is preliminary evidence available indicating that sympathetic nervous system disturbances are present in WAD. Decreased peripheral vasoconstriction in the hands, following a provocative manoeuvre of deep inspiration, has been shown in acute and chronic WAD when compared to health asymptomatic controls (Sterling, Jull, Vicenzino, et al., 2003), although the significance of these findings on recovery is not clear as this measure has not been shown to be associated with later physical or mental health outcomes (Sterling et al., 2006). In a small study (n = 20) of chronic WAD, reduced reactivity of the hypothalamic-pituitary adrenal axis, a closely interacting system to the autonomic system, has been demonstrated (Gaab et al., 2005). Decreased heart rate variability has also been found in participants with chronic WAD and showed a moderate association with pain and disability levels (Stone & Sterling, 2009). These findings of disturbances in various aspects of autonomic system functioning suggest that further investigation is warranted in order to elucidate what roles these processes play in WAD.

Some injured people may also be more likely to have genetic variants influencing stress-system function that increase the risk of acute and chronic pain. Perhaps the most well known of such variants are those related to the catechol-O-methyltransferase (COMT) enzyme. COMT is the primary enzyme that degrades catecholamines, including adrenaline and noradrenaline, and increased levels of catecholamines have been shown to produce allodynia and hyperalgesia (Nackley et al., 2007). Genetic variations located in the central haploblock of the gene encoding for COMT have been shown to influence COMT activity (Chen, Lipska, & Halim, 2004; Zhu, Lipsky, & Xu, 2004). Three common variations, or haplotypes, within this haploblock have been identified (Diatchenko et al., 2005). The LPS haplotype codes for the highest enzyme activity and is associated with the highest pain tolerance and reduced risk of acute (McLean et al., 2011) and chronic (Diatchenko et al., 2005) pain. The APS haplotype codes for comparably less enzyme activity and is associated with average pain tolerance. The HPS haplotype codes for the least enzyme activity and is associated with increased risk of chronic pain (Diatchenko et al., 2005). Preliminary data indicate that, in acute WAD, a COMT pain vulnerable genotype is associated with more severe neck pain, headache and dizziness and more dissociative symptoms assessed very early post-injury in the emergency department (McLean et al., 2011). It is yet to be determined if this genotype will be predictive of later recovery, but such findings would have important implications for the early management of whiplash injury. For example, the early targeting of physiological stress responses via medication such as propranolol has been shown to decrease pain in individuals with temporomandibular disorder and COMT HPS haplotype (Tchivilera et al., 2010), and such approaches could be beneficial in the management of WAD.

Recent data also indicate that stress-related responses may influence the physical presentation of individuals with WAD. Associations between the presence of hyperalgesia (lowered pain thresholds) and PTSD symptoms have been demonstrated (Sterling, Hendrikz, et al., 2011; Sterling & Kenardy, 2006). In a preliminary within-subject study, trauma-avoidance symptoms were shown to be associated with less activity in the subsequent hours following symptom recording (Sterling & Chadwick, 2010), indicating a possible influence of stress on motor activity/function. A subsequent study demonstrated an association between early PTSD symptoms (1-month post-injury) and later morphological muscle changes (fatty infiltrate identified with MRI) at 6 months post-injury (Elliott et al., 2011). These latter findings are intriguing and consistent with evidence that stress may have a detrimental effect on tissue healing (Walburn et al., 2009). The findings may also have implications for the management of WAD. Current clinical practice guidelines recommend the maintenance and encouragement of movement and activity (MAA, 2007; TRACsa, 2008), and the results of these studies suggest that addressing early stress responses may assist in achieving these goals of treatment. In summary, investigation of physiological stress-system responses and what role they play in health outcomes following whiplash injury is at an early stage. Nevertheless, if stress-system responses contribute to poor health outcomes following whiplash injury in vulnerable individuals, then treatments that attenuate these responses might be useful.

As with any painful musculoskeletal condition, relationships between psychosocial factors and health outcomes have been well documented, and this is no different for whiplash. It is generally considered that psychosocial factors do not, by themselves alone, fully explain poor recovery following the injury, but they likely interact with other processes and play a role in the persistence of symptoms. In the case of whiplash injury, some factors, including PTSD symptoms (Buitenhuis et al., 2006; Sterling et al., 2012), pain catastrophising (Walton et al., 2009) and negative expectations of recovery (Holm et al., 2008), have shown prognostic capacity in some studies. Other psychological factors including depression (Carroll, Liu, Holm, Cassidy, & Cote, 2011; Walton et al., 2009) and fear of movement (Pedler & Sterling, 2011; Williamson et al., 2008) have conflicting evidence for prognosis, with some studies showing an association with poor recovery and others finding no association.

Some authors have proposed that WAD should be considered in line with neck pain as a whole and should not be viewed as a different condition (Haldeman, Carroll, Cassidy, Schubert, & Nygren, 2008). However, differences between whiplash-initiated neck pain and non-traumatic type of neck pain have been demonstrated. As discussed earlier in this chapter, the sensory presentations of traumatic versus non-traumatic neck pain are different, suggesting variations in the central processing of nociceptive processes between the two types of neck pain (Chien et al., 2010; Elliott et al., 2008). Psychosocial differences are also present. WAD is initiated by a traumatic event, usually an MVC. PTSD is a common psychosocial sequelae following MVCs (Kuch, Cox, Evans, & Shulman, 1994), yet it is only recently that there has been increasing recognition of a shared pattern of aetiology between WAD and PTSD (McFarlane, Ellis, Barton, Browne, & Van Hooff, 2008). The effect of the distress surrounding the crash itself as opposed to, or in addition to, distress about neck pain may have a significant influence on outcome. Recent data indicate that PTSD symptoms are prevalent in individuals who have sustained whiplash injuries following motor vehicle accidents (Buitenhuis et al., 2006; Sterling, Kenardy, Jull, & Vicenzino, 2003; Sullivan et al., 2009). The early presence of PTSD symptoms have been shown to be associated with poor functional recovery from the injury (Buitenhuis et al., 2006; Sterling et al., 2005, 2012). The earlier presented Fig. 7.2 illustrated distinct recovery trajectories for PTSD following whiplash injury (Sterling et al., 2010). A significant proportion (10–25 %) of whiplash-injured individuals also meet the diagnostic criteria for PTSD in addition to the cardinal signs of neck pain (Buitenhuis et al., 2006; Jaspers, 1998; Mayou & Bryant, 2002), and this comorbidity of pain and PTSD may contribute to poor recovery following the injury.

The development of pain/disability and PTSD symptoms seems to be related, and research has begun to focus on the potential shared neurobiological pathways between PTSD and pain (Asmundson, Coons, Taylor, & Katz, 2002; McLean et al., 2005). In regard to research of WAD, in addition to PTSD symptoms predicting pain-related disability following injury, the reverse relationship also exists where initially higher pain levels predict later PTSD symptoms (Sterling, Hendrikz, et al., 2011). In this study, cold hyperalgesia also predicted both pain-related disability and PTSD symptoms (Sterling, Hendrikz, et al., 2011). Furthermore, it has been shown that the developmental trajectories for pain-related disability and PTSD symptoms occur mostly in synchrony (Sterling, Hendrikz, et al., 2011), as seen in Figs. 7.3 and 7.4. That is, there was a high probability (88 %) of an injured individual having a trajectory of low disability if their PTSD symptom trajectory was also at low levels. Conversely, there was a 75 % chance of having a resilient PTSD symptom trajectory if the disability trajectory was mild. Clinically, these findings suggest that, for trajectories of lower levels of disability, there is a good chance that the patient will show psychosocial resilience to the injury. The picture becomes less clear when disability trajectories are at higher levels. Nevertheless, in people with whiplash injury and initial or ongoing moderate to severe disability, clinicians should consider the possibility of PTSD symptoms being present in tandem at some level.

Further exploration of the relationship between pain-related disability and PTSD symptoms has been conducted in experimental studies. Interventions aimed at improving PTSD symptoms had been shown to also have effects on decreasing pain and disability. In a preliminary randomised controlled trial, Dunne et al. (2012b) showed that trauma-focussed cognitive-behaviour treatment, an evidence-based treatment for PTSD (NHMRC, 2007), resulted in clinically relevant changes in pain and disability, in addition to expected decreases in PTSD symptoms and PTSD diagnosis in patients with chronic WAD. In a later study, also in chronic WAD, it was shown that a trauma-cue exposure resulted in greater cold and mechanical hyperalgesia measured at sites over the cervical spine (Dunne, Kenardy, & Sterling, 2012a). Thus data are accumulating, demonstrating close relationships among the pain, disability and PTSD symptoms following whiplash injury.

Perceived injustice, defined as a cognitive appraisal characterised by a propensity to blame others for one’s current suffering and a tendency to exaggerate the severity and permanence of one’s injury-related losses (Sullivan et al., 2009), is a relatively new concept that, in view of the compensable nature of whiplash injury, would appear to be relevant. Initial investigations provide support for this proposal, where perceived injustice was the best single predictor of prolonged work absence after whiplash injury, even when controlling for variables of physical function (Sullivan et al., 2008). Further studies have shown that perceived injustice predicted the persistence of PTSD symptoms during a rehabilitation programme for chronic WAD (Sullivan et al., 2009) and that it moderated the relationship between pain and depressive symptoms (again in chronic WAD) (Scott & Sullivan, 2012). These studies have been cross-sectional in design, and further evaluation of the prognostic capacity of perceived injustice in an inception-cohort study is required. In summary, many of the pain-related psychosocial features shown to be present in other musculoskeletal conditions are involved in whiplash pain and disability. Additionally, psychosocial factors related to the injury or incident (MVC), namely PTSD symptoms, also appear to play an important role in the presentation and outcomes following whiplash injury.

There is little doubt that environmental and sociocultural factors contribute to the problem of whiplash. Depending upon the jurisdiction, many injured people will be required to engage with insurance, legal and health systems during their management process. It is generally considered that when an injured person receives compensation, then long-term health outcomes are worse (Cameron & Gabbe, 2009). However, more recently, the complexity of the issue surrounding compensation-related factors and health outcomes has become more recognised. Connelly and Spearing (2011) argue that there are numerous flaws surrounding studies investigating the role of compensation-related factors on health outcomes that require consideration. These include sample-selection bias, comparisons made between different jurisdictional compensation schemes and the case of reverse causality whereby the person with worse health outcomes is more likely to pursue a claim for compensation (Connelly & Spearing, 2011). Other authors also conclude that the quality of the evidence in this area is limited and that caution is required in the interpretation of study findings (Elbers, Hulst, Cuijpers, Akkermans, & Bruinvels, 2013). In a recent systematic review of the role of compensation-related factors on whiplash outcomes, it was concluded that there is no clear evidence to support the idea that compensation and its related processes lead to worse health (Spearing, Connelly, Gargett, & Sterling, 2012). In contrast to these findings, other studies have found that filing a claim for whiplash compensation is associated with subsequent poorer health outcomes, but that this effect occurs only in those with lesser symptoms, indicating a possible differential effect on subgroups of injured people (Sterling et al., 2010).

In summary on this vexing and emotive issue, Carroll, Connelly, et al. (2011) conclude that ‘Crucially, researchers and their audiences must also take care not to overgeneralize or confuse different aspects of WAD compensation. A study of one aspect of the compensation system cannot be used to draw conclusions about compensation as a whole, and because of the complexity of the compensation system and its intrinsic nature within a greater societal context, findings from one jurisdiction cannot necessarily be generalised to other jurisdictions’. Finally, as in other investigations exploring the complex question of how to prevent the transition to chronic WAD, in studying the role of compensation and compensation-related factors, it is important to retain a broad-based conceptualization of WAD and WAD recovery that includes recognition of the broad range of biological, psychological, societal, and economic factors that combine and interact to define and determine how people recover from WAD’.