Pain
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Neuropathic pain is a chronic disease resulting from dysfunction of the nervous system often due to peripheral nerve injury. Hypersensitivity to sensory stimuli (mechanical, thermal or chemical) is a common source of pain in patients and ion channels involved in detecting these stimuli are possible candidates for inducing and/or maintaining the pain. Transient receptor potential (TRP) channels expressed on nociceptors respond to different sensory stimuli and a few of them have been studied previously in the models of neuropathic pain. ⋯ Expression studies during development showed that TRPML3 is an embryonic channel that is induced upon nerve injury in three different nerve injury models investigated. Thus, the current results link for the first time a re-expression of TRPML3 with the development of neuropathic pain conditions. In addition, decreased mRNA levels after SNI were seen for TRPM6, TRPM8, TRPV1, TRPA1, TRPC3, TRPC4 and TRPC5.
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The sensitization of spinal dorsal horn neurones leads to prolonged enhancement of pain behaviour and can be evoked by intense C-fibre stimulation, tissue inflammation and peripheral nerve injury. Activation of central immune cells plays a key role in establishing pain hypersensitivity but the exact nature of the afferent input that triggers the activation of microglia and other glial cells within the CNS, remains unclear. Here intense but non-damaging, electrical stimulation of intact adult rat C-fibres for 5 min at 10 Hz induced central sensitization characterized by significant decreases in mechanical withdrawal thresholds 3, 24 and 48 h later. ⋯ Pre-treatment with minocycline (40 mg/kg, i.p.) prevented the C-fibre evoked sensitization and microglial activation. Identical C-fibre stimulation in 10-day old rat pups failed to activate microglia or change behaviour. These results demonstrate that a brief period of low frequency C-fibre stimulation, in the absence of nerve damage, is sufficient to activate microglia resulting in behavioural hyperalgesia.