Pain
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Complex regional pain syndrome (CRPS) is characterized by persistent and severe pain after trauma or surgery; however, its molecular mechanisms in the peripheral nervous system are poorly understood. Using proteomics, we investigated whether injured peripheral nerves of CRPS patients have altered protein profiles compared with control nerves. We obtained nerve samples from 3 patients with CRPS-2 who underwent resection of part of an injured peripheral nerve. ⋯ Furthermore, expression of S100 as a marker for Schwann cells, and neurofilament M as a marker of axons was comparable in both CRPS-2 and controls. Metallothioneins are zinc-binding proteins that are probably involved in protection against injury and subsequent regeneration after CNS damage. Their absence from the injured peripheral nerves of patients with CRPS-2 suggests a potential pathogenic role in generating pain in the damaged peripheral nerves.
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A motor unit consists of a motoneurone and the multiple muscle fibres that it innervates, and forms the final neural pathway that influences movement. Discharge of motor units is altered (decreased discharge rate and/or cessation of firing; and increased discharge rate and/or recruitment of new units) during matched-force contractions with pain. This is thought to be mediated by nociceptive (pain) input on motoneurones, as demonstrated in animal studies. ⋯ Discharge rate of motor units decreased during pain (P<.001) and anticipation (P<.01) compared with control contractions. De-recruitment of 1 population of units and new recruitment of another population were observed during both anticipation and pain; some changes in motor unit recruitment persisted after pain ceased. This challenges the fundamental theory that pain-related changes in muscle activity result from direct nociceptor discharge, and provides a mechanism that may underlie long-term changes in movement/chronicity in some musculoskeletal conditions.
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The dose-limiting side effect of taxane, platinum-complex, and other kinds of anticancer drugs is a chronic, distal, bilaterally symmetrical, sensory peripheral neuropathy that is often accompanied by neuropathic pain. Work with animal models of these conditions suggests that the neuropathy is a consequence of toxic effects on mitochondria in primary afferent sensory neurons. If this is true, then additional mitochondrial insult ought to make the neuropathic pain worse. ⋯ Chemotherapy-evoked painful peripheral neuropathy is associated with an abnormal spontaneous discharge in primary afferent A fibers and C fibers. Oligomycin, at the same dose that exacerbated allodynia and hyperalgesia, significantly increased the discharge frequency of spontaneously discharging A fibers and C fibers in both paclitaxel-treated and oxaliplatin-treated rats, but did not evoke any discharge in naïve control rats. These results implicate mitochondrial dysfunction in the production of chemotherapy-evoked neuropathic pain and suggest that drugs that have positive effects on mitochondrial function may be of use in its treatment and prevention.
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Cancer pain is one of the most severe types of chronic pain, and the most common cancer pain is bone cancer pain. The treatment of bone cancer pain remains a clinical challenge. Here, we report firstly that A-type K(+) channels in dorsal root ganglion (DRG) are involved in the neuropathy of rat bone cancer pain and are a new target for diclofenac, a nonsteroidal anti-inflammatory drug that can be used for therapy for this distinct pain. ⋯ Repeated diclofenac administration decreased soft tissue swelling adjacent to the tumor and attenuated bone destruction. These results indicate that peripheral A-type K(+) channels were involved in the neuropathy of rat bone cancer pain. Targeting A-type K(+) channels in primary sensory neurons may provide a novel mechanism-based therapeutic strategy for bone cancer pain.