Upregulation of Inflammatory Mediators in a Model of Chronic Pain after Spinal Cord Injury

Abstract

Chronic neuropathic pain is a disabling condition observed in large number of individuals following spinal cord injury (SCI). Recent progress points to an important role of neuroinflammation in the pathogenesis of central neuropathic pain. The focus of the present study is to investigate the role of proinflammatory molecules IL-1β, TNF-α, MCP-1, MMP-9 and TIMP-1 in chronic neuropathic pain in a rodent model of SCI. Rats were subjected to spinal cord contusion using a controlled linear motor device with an injury epicenter at T10. The SCI rats had severe impairment in locomotor function at 7 days post-injury as assessed by the BBB score. The locomotor scores showed significant improvement starting at day 14 and thereafter showed no further improvement. The Hargreaves’ test was used to assess thermal hyperalgesia for hindpaw, forepaw and tail. A significant reduction in withdrawal latency was observed for forepaw and tail of SCI rats at days 21 and 28, indicating the appearance of thermal hyperalgesia. Changes in expression of mRNAs for IL-1β, TNF-α, MCP-1, MMP-9 and TIMP-1 were assessed using real-time polymerase chain reaction in spinal cord including the injury epicenter along with regions above and below the level of lesion at day 28 post-injury. A significant increase was observed in the expression of MCP-1, TNF-α, TIMP-1 and IL-1β in the injury epicenter, whereas only TIMP-1 was upregulated in the area below the injury epicenter. The results of the study suggest that prolonged upregulation of inflammatory mediators might be involved in chronic neuropathic pain in SCI, and that TIMP-1 may play a role in maintenance of chronic below level pain.

Spontaneous Recovery of Reflex Voiding Following Spinal Cord Injury Mediated by Anti-inflammatory and Neuroprotective Factors

“…SCI is known to elicit an inflammatory response that recruits macrophages to the injured spinal cord and bladder, as indicated by reports of increased spinal cord levels of CCL2 chemokine that is chemotactic for macrophages, at 6 hours and also at 4 weeks 21 after SCI . Here, we report that pro-inflammatory CCL2 was also upregulated in bladder of SCI animals together with CX3CL1, CXCL-1, CXCL2 and CXCL-10 at 4, 8 and 12 weeks.…”

The Major Brain Endocannabinoid 2-AG Controls Neuropathic Pain and Mechanical Hyperalgesia in Patients with Neuromyelitis Optica

“…Central neuroinflammation is supposed to be one key mediator of thermal hyperalgesia and allodynia in experimental autoimmune encephalitis [71]. Additionally, after experimental spinal cord injury, the development of central neuropathic pain was associated with the upregulation of several proinflammatory cytokines [72] as well as other proteins such as S100ß, glial fibrilary acidic protein (GFAP), and AQP-4 [73], the latter representing the target antigen in NMO [7]. Elevation of these proteins persisted for at least 9 months in rodents with central neuropathic pain, while animals that did not develop central neuropathic pain after spinal cord injury did not up-regulate AQP-4 neither in the acute nor in the chronic stage of the disease [73].…”

Chronic post-traumatic headache: clinical findings and possible mechanisms

“…Similarly, dysfunctional glial cells in the vicinity of damaged neurons in animal models of central pain were suggested to secrete pro-inflammatory cytokines and other sensitizing agents, creating persistent glial inflammation and continual sensitization of neurons. [72][73][74] Perhaps, similar processes occurring in the brain after TBI underlie CPTHA.…”