Articles: hyperalgesia.
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Int J Hyg Environ Health · Mar 2013
Multiple chemical sensitivity: on the scent of central sensitization.
Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by recurrent, non-specific symptoms in response to chemically unrelated exposures in non-toxic concentrations. Although the pathophysiology of MCS remains unknown, central sensitization may be an important factor contributing to the clinical manifestations. ⋯ Increased capsaicin-induced secondary punctate hyperalgesia was demonstrated in MCS patients without comorbid, overlapping disorders, suggesting facilitated central sensitization in MCS.
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The role of mitogen-activated protein kinase (MAPK) family has been well defined in neuropathic pain. Ras and c-Raf constitute an important part of MAP kinase family as Ras/Raf/MEK/ERK2 signaling cascade. The present study was designed to investigate the analgesic potential of farnesyl thiosalicylic acid, a novel Ras inhibitor, and GW 5074, a selective c-Raf1 inhibitor, in chronic constriction-induced injury (CCI)-induced peripheral neuropathic pain. ⋯ Nerve ligature-induced CCI produced significant neuropathic pain manifestations in terms of cold and mechanical allodynia, and mechanical hyperalgesia. Single intrathecal administration of farnesyl thiosalicylic acid (5 and 10 μg) as well as GW 5074 (2 and 4 μg) significantly attenuated CCI-induced hyperalgesia and allodynia. The analgesic effects of farnesyl thiosalicylic acid and GW 5074 in CCI model suggests that pharmacological inhibition of Ras and c-Raf-1 signaling may be potentially useful for managing neuropathic pain.
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Fatty acid ethanolamides (FAEs), which include palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), are endogenous agonists of peroxisome proliferator-activated receptor-α (PPAR-α) and important regulators of the inflammatory response. They are degraded in macrophages by the lysosomal cysteine amidase, N-acylethanolamine acid amidase (NAAA). Previous studies have shown that pharmacological inhibition of NAAA activity suppresses macrophage activation in vitro and causes marked anti-inflammatory effects in vivo, which is suggestive of a role for NAAA in the control of inflammation. ⋯ ARN077 reversed these biochemical effects. The results identify ARN077 as a potent inhibitor of intracellular NAAA activity, which is active in vivo by topical administration. The findings further suggest that NAAA regulates peripheral pain initiation by interrupting endogenous FAE signaling at PPAR-α.
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Journal of neurology · Mar 2013
Comparative StudyPeripheral nociceptor sensitization mediates allodynia in patients with distal symmetric polyneuropathy.
Patients with painful neuropathy frequently complain of pain in response to normally non-painful brushing, namely dynamic mechanical allodynia. Despite many animal studies suggesting that allodynia arises when the spontaneous firing in damaged nociceptive afferents sensitise second-order nociceptive neurons to Aβ-fibre input, no studies have sought to confirm this mechanism by investigating Aβ-fibre sparing in human patients with allodynia. ⋯ Whereas no statistical difference was found in nerve conduction study data between patients with and without allodynia, LEP amplitudes were larger in patients with allodynia than in those without (P < 0.01 by Mann-Whitney U test). The lack of difference in NCS data between patients with and without allodynia suggest that this type of pain, rather than arising through second-order nociceptive neuron sensitization to Aβ-fibre input, might reflect a reduced mechanical threshold in sensitised intraepidermal nociceptive nerve terminals.