Pain
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Peripheral nerve injury may lead to neuropathic pain, which is often associated with mechanical and thermal allodynia, ectopic discharge of from injured nerves and from the dorsal root ganglion neurons, and elevated levels of proinflammatory cytokines, particularly interleukin-1 (IL-1). In the present study, we tested the role of IL-1 in neuropathic pain models using two mouse strains impaired in IL-1 signaling: Deletion of the IL-1 receptor type I (IL-1rKO) and transgenic over-expression of the IL-1 receptor antagonist (IL-1raTG). Neuropathy was induced by cutting the L5 spinal nerve on one side, following which mechanical and thermal pain sensitivity was measured. ⋯ WT mice developed progressive autotomy, beginning at 7 days post-injury, whereas the mutant strains displayed delayed onset of autotomy and markedly reduced severity of the autotomy score. Electrophysiological assessment revealed that in WT mice a significant proportion of the dorsal root axons exhibited spontaneous ectopic activity at 1, 3, and 7 days following spinal nerve injury, whereas in IL-1rKO and IL-1raTG mice only a minimal number of axons exhibited such activity. Taken together, these results suggest that IL-1 signaling plays an important role in neuropathic pain and in the altered neuronal activity that underlies its development.
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Promising recent developments in the therapeutic value of neuropeptide antagonists have generated renewed importance in understanding the functional role of neuropeptides in nociception and inflammation. To explore this relationship we examined behavioral changes and primary afferent neuronal plasticity following deep tissue inflammation. One hour following craniofacial muscle inflammation ipsilateral as well as contralateral head withdrawal thresholds and ipsi- and contralateral hindpaw withdrawal thresholds were lowered and remained reduced for 28 days. ⋯ Local injection of CGRP antagonist directly into the masseter muscle prior to CFA produced similar, but less pronounced, effects. These findings indicate that unilateral craniofacial muscle inflammation produces mechanical allodynia at distant sites and upregulates CGRP and SP in primary afferent neurons innervating deep tissues. These data further implicate CGRP and SP in deep tissue nociceptive mechanisms and suggest that peptide antagonists may have therapeutic potential for musculoskeletal pain.
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Low back pain (LBP) is a common symptom among adults but little is known about its persistence over time in defined populations. The aim of this study was to examine the persistence of LBP among a cohort of industrial employees studied in four successive surveys during a total of 28 years. Cross-tabulations and logistic regression was used to estimate the interdependence of LBP occurrence at the surveys. ⋯ The odds ratio of local LBP at the 5-, 10-, or 28-year follow-up for those with such pain at baseline vs. not were 6.0 (95% CI 4.3-8.3), 4.7 (3.3-6.6) and 4.0 (2.6-6.3), adjusted for age, gender and occupational class. The respective figures for radiating LBP were 8.5 (5.7-12.5), 6.7 (4.4-10.1) and 2.3 (1.5-3.6). We conclude that LBP is commonly recurrent.