Articles: neuralgia.
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Despite requiring successful trials prior to implantation, spinal cord stimulation (SCS) systems for pain are often later removed. Removing surgically implanted hardware subjects patients to the risks and discomfort of a second surgery, threatens the cost-effectiveness of SCS, and limits the perceived durability of SCS technology for pain problems. ⋯ Inadequate pain control is the most common reason for SCSES. Advances in technology are needed to improve the quality and duration of pain control, as well as to design improvements to make the hardware more comfortable. A significant number of implants are removed due to need for MRI, a fact obviating the need for MRI-compatible systems. Patients considering SCS paddle lead placement should be counseled on the most common reasons for later explantation.
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Caloric restriction (CR) increases both average and maximum lifespan, retards physiological signs of ageing, and delays the onset of several diseases and may mediate neuropathic pain. Neuropathic pain seriously affects the quality of life of patients. In this study, we investigated whether CR exerts anti-nociceptive effects on neuropathic pain, and probed its potential mechanisms. ⋯ These results suggest that the effects of CR on pain behaviours in a rat model of nerve injury are via inhibition of excessive neuro-inflammation induced by the injury. CR may be of benefit in patients with neuropathic pain.
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Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a serious dose-limiting neurotoxic effect of cancer drug treatment. The underlying mechanism(s) of this debilitating condition, which lacks effective drug treatment, is incompletely understood. However, neural-immune interactions, involving increased expression and release of cytokines, are believed to be involved. Here, we examined, in the paclitaxel rat model of CIPNP, whether plasma levels of 24 cytokines/chemokines change after paclitaxel treatment, and whether blocking of signalling of some of those cytokines would reverse/attenuate behavioural signs of CIPNP. ⋯ This study demonstrates that paclitaxel-treated rats exhibit, in addition to indices of mechanical and cold hypersensitivity, a behavioural sign of spontaneous pain, the principal compliant of patients with neuropathic pain. This was accompanied by upregulation in plasma levels of key cytokines/chemokines (IL-1α, IL-1β, IL-6, TNF-α, INF-γ and MCP-1) 31 days post-treatment. However, it is noteworthy that cytokine release, rather than nerve injury per se, may be causative of NP in this model of CIPNP. Nevertheless, our findings that pharmacological blockade of TNF-α, IL-1β and MCP-1 attenuated both evoked and spontaneous pain suggest that strategies that target inhibition of these cytokines may be effective in treating CIPNP.
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Pregabalin is a first-line agent for neuropathic pain treatment whose abuse liability remains controversial. Surprisingly, studies exploring the reinforcing properties of pregabalin in operant mouse models are missing. ⋯ This study shows that mice with a nerve injury self-administer pregabalin at doses effective reducing nociceptive hypersensitivity and depressive-like behaviour associated with the neuropathic pain model. Interestingly, mice without neuropathy also develop operant self-administration behaviour, suggesting potential abuse liability of this first-line drug for neuropathic pain treatment.
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Journal of neurochemistry · Apr 2018
Early CALP2 expression and microglial activation are potential inducers of spinal IL-6 up-regulation and bilateral pain following motor nerve injury.
Previous work from our laboratory showed that motor nerve injury by lumbar 5 ventral root transection (L5-VRT) led to interleukin-6 (IL-6) over-expression in bilateral spinal cord, and that intrathecal administration of IL-6 neutralizing antibody delayed the induction of mechanical allodynia in bilateral hind paws. However, early events and upstream mechanisms underlying spinal IL-6 expression following L5-VRT require elucidation. The model of L5-VRT was used to induce neuropathic pain, which was assessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats. ⋯ Depletion of microglia using Mac-1-saporin partially prevented IL-6 up-regulation and attenuated VRT-induced bilateral mechanical allodynia. Taken together, our findings provide evidence that increased spinal cord CALP2 and microglia cell activation may have early causative roles in IL-6 over-expression following motor nerve injury. Agents that inhibit CALP2 and/or microglia activation may therefore prove valuable for treating neuropathic pain.