The Shared Neuroanatomy and Neurobiology of Comorbid Chronic Pain and PTSD

Abstract

Chronic pain and posttraumatic stress disorder (PTSD) are disabling conditions that affect biological, psychological, and social domains of functioning. Clinical research demonstrates that patients who are affected by chronic pain and PTSD in combination experience greater pain, affective distress, and disability than patients with either condition alone. Additional research is needed to delineate the interrelated pathophysiology of chronic pain and PTSD, with the goal of facilitating more effective therapies to treat both conditions more effectively; current treatment strategies for chronic pain associated with PTSD have limited efficacy and place a heavy burden on patients, who must visit various specialists to manage these conditions separately. This article focuses on neurobiological factors that may contribute to the coprevalence and synergistic interactions of chronic pain and PTSD. First, we outline how circuits that mediate emotional distress and physiological threat, including pain, converge. Secondly, we discuss specific neurobiological mediators and modulators of these circuits that may contribute to chronic pain and PTSD symptoms. For example, neuropeptide Y, and the neuroactive steroids allopregnanolone and pregnanolone (together termed ALLO) have antistress and antinociceptive properties. Reduced levels of neuropeptide Y and ALLO have been implicated in the pathophysiology of both chronic pain and PTSD. The potential contribution of opioid and cannabinoid system factors also will be discussed. Finally, we address potential novel methods to restore the normal function of these systems. Such novel perspectives regarding disease and disease management are vital to the pursuit of relief for the many individuals who struggle with these disabling conditions.

Potential neurobiological benefits of exercise in chronic pain and posttraumatic stress disorder: Pilot study

“…As reviewed by Scioli-Salter et al [13], pain can trigger memories as well as emotional and physiological reexperiencing of a trauma by activating the amygdala via sensory projections routed through the thalamus and parabrachial nucleus. Activation of the amygdala, in turn, can affect pain sensitivity by increasing molecular substrates in the dorsal horn of the spinal cord that facilitate transmission of pain from the periphery.…”

“…Across biological systems, NPY is known to raise the threshold for release of neurotransmitters with which it is localized by acting at inhibitory presynaptic NPY-Y 2 receptors [21], suggesting that this mechanism may contribute to its possible acute antinociceptive effects. Effects at upregulated NPY-Y 1 receptors in the spinal cord in response to acute pain are, in turn, thought to prevent progression of acute pain to chronic pain [13].…”

“…As detailed in a recent review [13], potential pathophysiologic factors shared between chronic pain and PTSD include deficits in neuropeptide Y (NPY) and the neuroactive gamma-aminobutyric acid (GABA)-ergic steroids allopregnanolone and its equipotent stereoisomer pregnanolone (together termed ALLO) [14][15][16][17][18][19][20]. These antinociceptive and stress-buffering molecules have been found to be low in patients with PTSD and inversely correlated with PTSD symptom severity [14][15][16][17][18][19][20][21][22][23][24][25].…”

Post-traumatic stress disorder and temporomandibular dysfunction: a review and clinical implications

“…Both conditions share somatic hypervigilance, dodge behavior, high levels of fear and arousal to traumatic stimuli, suffering and dysregulation of the stress system 28,39 . Some theoretical models have been proposed to explain the relationship between chronic pain and PTSD [10][11][12] , although none presents significant empirical support. The mutual maintenance model proposed by Sharp and Harvey is the most widespread 10 .…”

“…In addition, the comorbidity relationship between TMD and PTSD may be a complicating factor for TMD handling, as it reduces the efficacy of commonly used therapeutic interventions 9 . The clinically observable relationship's reasons between TMD and PTSD are not fully understood, but some theoretical models have been proposed to explain the relationship between chronic pain and PTSD [10][11][12] . Among them, the mutual maintenance model 10 is the most widespread and suggests that components related to PTSD and painful condition exacerbate and maintain one another.…”