Matrix metalloproteinases (MMPs) emerge as modulators of neuropathic pain. Because myelin protects Aβ afferents from ectopic hyperexcitability and nociception from innocuous mechanical stimuli (or mechanical allodynia), we analyzed the role of MMPs in the development of mechanical allodynia through myelin protein degradation after rat and MMP-9−/− mouse L5 spinal nerve crush (L5 SNC). MMPs were shown to promote selective degradation of myelin basic protein (MBP), with MMP-9 regulating initial Schwann cell-mediated MBP processing after L5 SNC. Acute and long-term therapy with GM6001 (broad-spectrum MMP inhibitor) protected from injury-induced MBP degradation, caspase-mediated apoptosis, macrophage infiltration in the spinal nerve and inhibited astrocyte activation in the spinal cord. The effect of GM6001 therapy on attenuation of mechanical allodynia was robust, immediate and sustained through the course of L5 SNC. In conclusion, MMPs mediate the initiation and maintenance of mechanical nociception through Schwann cell-mediated MBP processing and support of neuroinflammation.

Peripheral nerve regeneration begins immediately after injury. Understanding the mechanisms by which early modulators of axonal degeneration regulate neurite outgrowth may affect the development of new strategies to promote nerve repair. Tumor necrosis factor-α (TNF-α) plays a crucial role in the initiation of degenerative cascades after peripheral nerve injury. Here we demonstrate using real-time Taqman quantitative RT-PCR that, during the time course (days 1–60) of sciatic nerve crush, TNF-α mRNA expression is induced at 1 day and returned to baseline at 5 days after injury in nerve and the corresponding dorsal root ganglia (DRG). Immediate therapy with the TNF-α antagonist etanercept (fusion protein of TNFRII and human IgG), administered systemically (i.p.) and locally (epineurially) after nerve crush injury, enhanced the rate of axonal regeneration, as determined by nerve pinch test and increased number of characteristic clusters of regenerating nerve fibers distal to nerve crush segments. These fibers were immunoreactive for growth associated protein-43 (GAP-43) and etanercept, detected by anti-human IgG immunofluorescence. Increased GAP-43 expression was found in the injured nerve and in the corresponding DRG and ventral spinal cord after systemic etanercept compared with vehicle treatments. This study established that immediate therapy with TNF-α antagonist supports axonal regeneration after peripheral nerve injury.

Background:Traction apophysitis of medial epicondyle (MEC) lesions and osteochondritis dissecans (OCD) of the capitellum are common elbow injuries in adolescent baseball players. However, the age-specific prevalence of these pathologies and their influence on elbow pain remain unknown.Purpose:To investigate the age-specific prevalence of each MEC lesion and capitellar OCD and to identify the incidence of elbow pain in each condition.Study Design:Descriptive epidemiology study.Methods:Study participants consisted of 4249 baseball players aged 6 to 17 years. A questionnaire was used to assess history of elbow pain, and morphological changes of the elbow joint were assessed using ultrasonography.Results:Regarding MEC lesions, fragmented (FG) and irregular (IR) lesions both reached their greatest respective prevalence at 11 to 12 years of age. After 14 years of age, IR decreased sharply, whereas FG was maintained at approximately 10%. Hypertrophic (HT) lesions increased sharply, reaching over 50% at 16 years of age, while there was a decrease in IR and FG lesions in the same age group. The prevalence of capitellar OCD remained the same (approximately 2%) throughout all ages except for in players aged 7 to 8 years (>7%). Players with MEC lesions had significantly greater prevalence of a history of elbow pain compared with those without (68.0% vs 39.1%) and were at a significantly greater risk for FG lesions (odds ratio [OR], 4.04; 95% CI, 3.16-5.22) compared with IR (OR, 3.22; 95% CI, 2.44-4.27) and HT lesions (OR, 2.03; 95% CI, 1.75-2.36). Players with capitellar OCD also had a significantly greater risk of a history of elbow pain (OR, 2.34; 95% CI, 1.40-4.11).Conclusion:Controlling the amount of practice and its intensity according to the condition of each player in the preadolescent and adolescent periods may be important in accelerating bony healing and decreasing preventable elbow pain in adulthood.