Chronic Pain After Traumatic Brain Injury: Pathophysiology and Pain Mechanisms

Irvine, Karen‐Amanda; Clark, J. David

doi:10.1093/pm/pnx153

Cited by 73 publications

(70 citation statements)

References 167 publications

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“…The estimated global yearly incidence of traumatic brain injury (TBI) is 106/100,000 capita, whereas it is around 600/100,000 capita in the case of mild TBI [57, 58]. Some 13 million people is estimated to live with disabilities related to TBI in Europe and the USA [59].…”

Section: Chronic Central Npmentioning

confidence: 99%

Therapeutic Approaches for Peripheral and Central Neuropathic Pain

et al. 2019

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Neuropathic pain is a chronic secondary pain condition, which is a consequence of peripheral or central nervous (somatosensory) system lesions or diseases. It is a devastating condition, which affects around 7% of the general population. Numerous etiological factors contribute to the development of chronic neuropathic pain. It can originate from the peripheral part of the nervous system such as in the case of trigeminal or postherpetic neuralgia, peripheral nerve injury, painful polyneuropathies, or radiculopathies. Central chronic neuropathic pain can develop as a result of spinal cord or brain injury, stroke, or multiple sclerosis. As first-line pharmacological treatment options, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids are recommended. In trigeminal neuralgia, carbamazepine and oxcarbazepine are the first-choice drugs. In drug-refractory cases, interventional, physical, and psychological therapies are available. This review was structured based on a PubMed search of papers published in the field from 2010 until May 2019.

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Section: Chronic Central Npmentioning

confidence: 99%

Therapeutic Approaches for Peripheral and Central Neuropathic Pain

et al. 2019

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“…In the United States, more than 2.5 million injuries occur per year (Centers for Disease Control and Prevention, 2015), with the majority of these cases being mild in nature 3 . While many symptoms of mild TBI dissipate rapidly after injury, these patients frequently experience unusually high rates of acute and chronic pain 4,5 . Headache commonly occurs after TBI, although pain can be widespread and may include the back and extremities 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation

Sahbaie

Irvine

Liang

et al. 2019

Sci Rep

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High rates of acute and chronic pain are associated with traumatic brain injury (TBI), but mechanisms responsible for the association remain elusive. Recent data suggest dysregulated descending pain modulation circuitry could be involved. Based on these and other observations, we hypothesized that serotonin (5-HT)-dependent activation of spinal CXC Motif Chemokine Receptor 2 (CXCR2) may support TBI-related nociceptive sensitization in a mouse model of mild TBI (mTBI). We observed that systemic 5-HT depletion with p-chlorophenylalanine attenuated mechanical hypersensitivity seen after mTBI. Likewise, selective spinal 5-HT fiber depletion with 5,7-dihydroxytryptamine (5,7-DHT) reduced hypersensitivity after mTBI. Consistent with a role for spinal 5-HT3 serotonin receptors, intrathecal ondansetron administration after TBI dose-dependently attenuated nociceptive sensitization. Also, selective CXCR2 antagonist SCH527123 treatment attenuated mechanical hypersensitivity after mTBI. Furthermore, spinal CXCL1 and CXCL2 mRNA and protein levels were increased after mTBI as were GFAP and IBA-1 markers. Spinal 5,7-DHT application reduced both chemokine expression and glial activation. Our results suggest dual pathways for nociceptive sensitization after mTBI, direct 5-HT effect through 5-HT3 receptors and indirectly through upregulation of chemokine signaling. Designing novel clinical interventions against either the 5-HT3 mediated component or chemokine pathway may be beneficial in treating pain frequently seen in patients after mTBI.

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“…Structural and functional alterations affecting pain processing and the neuroendocrine modulation of pain may lead to an increased risk of chronic pain after TBI. 16,21 If risk of chronic pain increases with greater severity of injury to the brain, this would explain why our study found no associations of mTBI with future back pain, but did find associations with moderate to severe TBI. However, there are many other explanations other than a causal link, including those described above, which may partially or completely explain the moderate to severe TBIback pain association.…”

Section: Discussionmentioning

confidence: 59%

“…22,35 Various theoretical mechanisms may explain an increased risk of pain after TBI, including alterations in descending (inhibitory) regulation of pain, ascending pain pathways, dopamine signaling, neuroinflammation, neurodegenerative processes, diffuse axonal injury, synaptic dysfunction, and others. 16,21 Alternatively, the link between pain and TBI may be explained by shared risk factors for both conditions, such as major physical traumas causing both brain injury and musculoskeletal injury at the same time. To our knowledge, no prior longitudinal studies including a comparison group of those without TBI have been conducted to examine whether clinically defined TBI is a risk factor for specific chronic pain syndromes other than headache.…”

mentioning

confidence: 99%