European journal of pain : EJP
-
Current rodent models of neuropathic pain produce pain hypersensitivity in almost all lesioned animals and not all identified experimental effects are pain specific. 18G needlestick-nerve-injury (NNI) to one tibial nerve of outbred Sprague-Dawley rats models the phenotype of Complex Regional Pain Syndrome (CRPS), a post-traumatic neuropathic pain syndrome, leaving roughly half of NNI rats with hyperalgesia. We compared endoneurial data from these divergent endophenotypes searching for pathological changes specifically associated with pain-behaviors. Tibial, sural, and common sciatic nerves from 12 NNI rats plus 10 nerves from sham-operated controls were removed 14 days post-surgery for morphometric analysis. ⋯ Similar pathological changes have been identified in CRPS-I patients. The current findings suggest that severity of endoneurial vasculopathy and inflammation may correlate better with neuropathic pain behaviors than degree of axonal loss. Spread of pathological changes to nearby ipsilateral and contralateral nerves might potentially contribute to extraterritorial pain in CRPS.
-
Inflammatory and immune responses following nerve injury have been shown to play an important role in neuropathic pain. Lipoxins are endogenous lipoxygenase-derived eicosanoids performing protective roles in a range of pathophysiologic processes. Here, we examined the effects of intrathecal lipoxinA4 (LXA4) on NF-κB activation and pro-inflammatory cytokine (TNF-α, IL-1β and IL-6) expression in dorsal root ganglia (DRG) following chronic compression of DRG (CCD), a model of neuropathic pain. ⋯ CCD induced both mechanical allodynia and thermal hyperalgesia, and increased the expression of TNF-α, IL-1β, IL-6 and NF-κB. Intrathecal injection of LXA4 prevented the development of neuropathic pain and inhibited NF-κB activation and pro-inflammatory cytokine upregulation in a dose-dependent manner. In this study, we have shown the strong protective effect of intrathecal LXA4 on the development of nociceptive behaviors induced by CCD and that these effects might be associated with its anti-inflammatory and pro-resolution properties.
-
Recent studies suggest that CNS phospholipase A(2) (PLA(2) ) isoforms play a role in nociception, but until now, direct evidence of increased brain PLA(2) activity during allodynia or hyperalgesia is lacking. The present study was carried out, using lipidomics or systems wide analyses of lipids using tandem mass spectrometry, to elucidate possible changes in rat brain lipids after inflammatory pain induced by facial carrageenan injection. The caudal medulla oblongata showed decreases in phospholipids including phosphatidylethanolamine and phosphatidylinositol species, but increases in lysophospholipids, including lysophosphatidylethanolamine, lysophosphatidylinositol and lysophosphatidylserine, indicating increased PLA(2) activity and release of arachidonic acid after facial carrageenan injection. ⋯ Increase in sPLA(2) -III mRNA expression was found in the caudal medulla of carrageenan-injected rats, although no difference in sPLA(2) -III protein expression was detected. The changes in lipids as determined by lipidomics were therefore consistent with an increase in PLA(2) enzyme activity, but no change in enzyme protein expression. Together, these findings indicate enhanced PLA(2) activity in the caudal medulla oblongata after inflammatory orofacial pain.
-
Investigating possible psychosocial predictors of unexplained chronic pain in adolescents is crucial in understanding its development and prevention. A general population sample of adolescents (n = 2230) from the TRAILS cohort study was investigated longitudinally to assess the influence of maternal vulnerability, in terms of anxiety, depression and stress, and parenting stress at age 10-12 years, on the presence of chronic pain at age 12-15 years. Of these adolescents, 269 (12.9%) reported experiencing chronic pain, of which 77% reported severe chronic pain and 22% reported multiple chronic pain. ⋯ Subgroup analyses showed similar results for adolescents with severe chronic pain. Mediation analyses indicated that parenting stress mediates the effect between maternal anxiety, or stress, and chronic pain. The findings suggest that interventions to diminish maternal feelings of anxiety and stress, while in turn adjusting maternal behaviour, may prevent the development of chronic pain in adolescence.