Neurobiological Mechanisms of Whiplash
Samuel A. McLean
Among individuals involved in one of the fifty million motor vehicle collisions (MVCs) that occur worldwide each year [37], persistent musculoskeletal pain is a common and costly public health problem [7]. The purpose of this chapter is to provide a contemporary understanding of neurobiological mechanisms mediating persistent symptom development after MVC. The past two decades have witnessed the increasing application of molecular techniques to gain insight into the pathogenesis of post-MVC pain. However, the most important advance in understanding neurobiological mechanisms mediating post-MVC pain outcomes has been the evolution to a more accurate and complete characterization of the phenotype. This is of critical importance because if the phenotype is not accurately characterized, then it is unlikely that any amount of application of bioinformatic, statistical, or “omics” techniques will yield valid information. Candidate neurobiological systems responsible for the pathogenesis of post-MVC neuropsychiatric sequelae will then be reviewed, with an emphasis on those domains most fruitful for future study.
EVOLUTION TO A MORE ACCURATE UNDERSTANDING OF THE POST-MVC PAIN PHENOTYPEFrom Neck Pain to Neck Region Pain with Associated Symptoms
Studies of pain after MVC dating from as early as the 1950s focused on pain in the neck region [19], and cases of post-MVC pain were attributed to “whiplash injury” of the neck [19, 23, 40]. Consistent with this hypothesis, studies evaluating neurobiological mechanisms of post-MVC pain pathogenesis focused almost exclusively on the neck. In 1995, the Quebec Task Force on Whiplash-Associated Disorders changed the term from whiplash to “Whiplash-Associated Disorders” [42]. This change in terminology was made because (1) it was recognized that pain was not limited to the neck region (although additional areas of pain were believed to be limited to adjacent regions), and (2) it had become apparent that not only pain but also cognitive and somatic symptoms were frequent components of the syndrome [42]. (Of note, the association between cognitive symptoms and head injury has been shown to be extremely weak [8].) Even after the Quebec Task Force, most of the research into biological mechanisms mediating persistent post-MVC pain continued to be based on the hypothesis that biological mechanisms mediating post-MVC pain were due to neck injury during MVC.
From Pain in the Neck Region to Pain Potentially Occurring in Many Body Regions as Part of a Frequently Multidimensional Posttraumatic Neuropsychiatric Disorder
More recently, large-scale studies have shown that pain after MVC may occur in many different body regions (e.g., low back [9]), and/or may be widespread [25, 26, 50, 51]. For example, in one recent study of 948 individuals enrolled in the emergency department (ED) in the immediate aftermath of MVC, pain outside of the neck region at the time of ED evaluation was the norm, and 22% had pain in 7 or more body regions
[33]. At 6 weeks, moderate or severe low back pain was as common as neck pain (with a prevalence of 37% for each) and overlapped with neck pain in only 23% of patients [4]. Further, pain across all body regions accounted for nearly twice as much of the variance in pain interference as neck pain alone (60% vs. 34%). Similarly, in two large cohorts of individuals experiencing MVC who presented to the ED after MVC and were discharged to home after evaluation, 6 weeks after MVC, 528/859 (61.5%) of European Americans reported MVC-related pain outside body areas considered “whiplash-related” (head, neck, shoulders, and upper back), and 562/668 (84.1%) of African Americans reported pain outside such areas (unpublished data). Together, these data demonstrate that pain in body regions other than “whiplash-associated disorders” regions are very common after MVC and contribute substantially to overall pain-related disability. Thus, evaluating neck pain alone poorly characterizes the patient’s pain experience. Along with these increasing data that pain often occurs across many regions after MVC, and is frequently widespread, evidence has also continued to accrue that post-MVC pain often occurs in the context of other symptoms. For example, Dr. Michele Sterling and others have shown that pain after MVC, and PTSD symptoms after MVC are often comorbid [17, 44, 45], and depressive symptoms have also been shown to be frequently comorbid with post-MVC pain [6, 22, 35], along with a wide variety of somatic symptoms [36].
[33]. At 6 weeks, moderate or severe low back pain was as common as neck pain (with a prevalence of 37% for each) and overlapped with neck pain in only 23% of patients [4]. Further, pain across all body regions accounted for nearly twice as much of the variance in pain interference as neck pain alone (60% vs. 34%). Similarly, in two large cohorts of individuals experiencing MVC who presented to the ED after MVC and were discharged to home after evaluation, 6 weeks after MVC, 528/859 (61.5%) of European Americans reported MVC-related pain outside body areas considered “whiplash-related” (head, neck, shoulders, and upper back), and 562/668 (84.1%) of African Americans reported pain outside such areas (unpublished data). Together, these data demonstrate that pain in body regions other than “whiplash-associated disorders” regions are very common after MVC and contribute substantially to overall pain-related disability. Thus, evaluating neck pain alone poorly characterizes the patient’s pain experience. Along with these increasing data that pain often occurs across many regions after MVC, and is frequently widespread, evidence has also continued to accrue that post-MVC pain often occurs in the context of other symptoms. For example, Dr. Michele Sterling and others have shown that pain after MVC, and PTSD symptoms after MVC are often comorbid [17, 44, 45], and depressive symptoms have also been shown to be frequently comorbid with post-MVC pain [6, 22, 35], along with a wide variety of somatic symptoms [36].
While patients experience coincident pain and somatic and/or psychological symptoms as part of one syndrome, most patients have each symptom type evaluated independently in compartmentalized, siloed clinical settings. An individual with persistent symptoms after MVC might, for example, see a psychiatrist for an evaluation of posttraumatic stress disorder and/or depressive symptoms, a neurologist for somatic symptoms labeled as “postconcussive,” and a physiatrist or anesthesiology pain medicine specialist for posttraumatic musculoskeletal pain. Similarly, research into biological mechanisms has also often been compartmentalized, with outcomes focused on one symptom domain or another. Better aligning neurobiological studies with the patient experience, by evaluating individuals according to multidimensional symptom cluster trajectory rather than symptom component, would
allow us to most accurately assess the neurobiological substrate of different multidimensional post-MVC syndromes.
allow us to most accurately assess the neurobiological substrate of different multidimensional post-MVC syndromes.
CANDIDATE BIOLOGICAL MECHANISMS MEDIATING POST-MVC OUTCOMESTissue Injury to Neck Structures
As described above, consistent with the pathophysiologic hypothesis that persistent symptoms after MVC result from abnormal neck motion, most studies evaluating neurobiological mechanisms of post-MVC pain pathogenesis have focused on the neck. A peripheral nociceptive input is capable of dynamically maintaining chronic pain over a broader local area [21]; tissue structures that might provide an ongoing source of nociceptive input are many, including the zygapophysial joint capsule, anuli fibrosi, and various ligaments, muscles, and intra-articular structures [12]. The best studied of these candidate structures is the zygapophysial joint. A small randomized controlled trial of radiofrequency neurotomy of zygapophysial joint cervical medial branch nerves in 24 patients with chronic neck pain after MVC found that the intervention group had substantially improved neck pain outcomes. In addition, several small, nonrandomized observational case series also suggest a potential treatment benefit [1, 30]. A transient peripheral tissue injury might also result in the development of persistent post-MVC pain, if this transient injury caused peripheral and/or central sensitization that then became self-sustaining. Whether such a phenomenon accounts for persistent post-MVC pain development in some individuals is unknown.
These data suggest that peripheral tissue injury may contribute to chronic post-MVC pain in some individuals. However, as already described, important features of common post-MVC symptom phenotypes are poorly explained by cervicogenic mechanisms, including the typical occurrence of pain in body regions distant from the neck, the common prevalence of widespread pain, and the often multidimensional nature of the phenotype, of which pain symptoms are only one part. In addition, if injury-related damage to cervical structures occurring at the
moment of MVC played a dominant role in the genesis of post-MVC pain symptoms, then in epidemiologic studies, collision-related characteristics (e.g., vehicle speed, direction of collision, amount of vehicle damage) would be expected to be important risk factors for chronic post-MVC pain development. In study after study, however, collision-related factors have consistently been shown to be poor predictors of post-MVC pain outcomes [3, 6, 7, 10, 11, 17, 24, 26, 33, 44, 45]. Biomechanical experts frequently argue that this lack of association is due to the inability of epidemiologic studies to capture all of the subtleties of individual crash histories, such as the degree of neck flexion or extension at the moment of impact, the degree of lateral rotation of the neck at the moment of impact, and the distance of the head from the car head restraint. This is not a valid reason to discount epidemiologic study results, however, for while no study evaluates every potentially relevant variable, unless a consistent relationship exists between an important unmeasured third variable and measured variable(s), the relationship between the measured variable and outcome is unaffected. For example, cigarette smoking has consistently been shown to be a dominant risk factor for lung cancer development even though epidemiologic studies identifying this association have never accounted for all of the subtleties of individual cigarette smoking histories, such as cigarette brand, proportion of time spent smoking indoors versus outdoors, method of holding cigarette and inhaling, proportion of time that smoker tends to leave cigarette burning in ashtray versus smoking, secondhand smoke exposure, etc. If MVC-related tissue injury played a central role in the pathogenesis of post-MVC pain, then collision-related factors should be dominant predictors of pain outcomes. But they are not.
moment of MVC played a dominant role in the genesis of post-MVC pain symptoms, then in epidemiologic studies, collision-related characteristics (e.g., vehicle speed, direction of collision, amount of vehicle damage) would be expected to be important risk factors for chronic post-MVC pain development. In study after study, however, collision-related factors have consistently been shown to be poor predictors of post-MVC pain outcomes [3, 6, 7, 10, 11, 17, 24, 26, 33, 44, 45]. Biomechanical experts frequently argue that this lack of association is due to the inability of epidemiologic studies to capture all of the subtleties of individual crash histories, such as the degree of neck flexion or extension at the moment of impact, the degree of lateral rotation of the neck at the moment of impact, and the distance of the head from the car head restraint. This is not a valid reason to discount epidemiologic study results, however, for while no study evaluates every potentially relevant variable, unless a consistent relationship exists between an important unmeasured third variable and measured variable(s), the relationship between the measured variable and outcome is unaffected. For example, cigarette smoking has consistently been shown to be a dominant risk factor for lung cancer development even though epidemiologic studies identifying this association have never accounted for all of the subtleties of individual cigarette smoking histories, such as cigarette brand, proportion of time spent smoking indoors versus outdoors, method of holding cigarette and inhaling, proportion of time that smoker tends to leave cigarette burning in ashtray versus smoking, secondhand smoke exposure, etc. If MVC-related tissue injury played a central role in the pathogenesis of post-MVC pain, then collision-related factors should be dominant predictors of pain outcomes. But they are not.
Related posts:
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Pain Signaling Systems from Injured Cervical Facet Joints
How Do We Prevent the Transition from Acute to Chronic Pain After Whiplash Injury?
What is Needed to Establish Valid Predictors of WAD Recovery?
The Clinical Examination for Risk Factors in Whiplash Trauma
Improving Psychologically Oriented Treatments for WAD
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