Pain
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Some forms of chronic pain are thought to be driven and maintained by nociceptive input, which can drive plasticity within nociceptive pathways. We have previously identified abnormalities along the entire nociceptive pathway in chronic myalgic temporomandibular disorders (mTMD), including the trigeminal nerves, brainstem pathways, and in the thalamus and somatosensory cortex. These data suggest that there is a peripheral nociceptive drive in mTMD, but the source of this nociceptive activity remains unknown. ⋯ These findings were consistent across 2 independent cohorts of 17 mTMD patients, compared to 17 age- and sex-matched controls. We propose a model where reduced TAC-to-muscle ratio could result in a predisposition to muscle tissue injury. In sum, abnormalities of the temporalis muscles in mTMD supports our hypothesis that chronic mTMD pathophysiology may be related to peripheral nociceptive barrage originating from the muscles of mastication.
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Transcribed ultraconserved regions are a novel class of long noncoding RNAs and are completely conserved in humans, rats, and mice. Transcribed ultraconserved regions have been implicated in diverse biological processes; however, very little is currently known about their role in pain modulation. Here, we found that the level of the spinal transcribed ultraconserved region uc.153 was significantly increased in a mouse model of sciatic nerve chronic constriction injury (CCI)-induced chronic neuropathic pain. ⋯ By contrast, the overexpression of spinal uc.153 produced pain behaviours and neuronal sensitization in naive mice. Moreover, we found that uc.153 participates in the regulation of neuropathic pain by negatively modulating the processing of pre-miR-182-5p. Collectively, our findings reveal an important role for uc.153 in pain modulation and provide a novel drug target for neuropathic pain therapy.
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Previous studies have shown that the peripheral nerve regeneration process is linked to pain in several neuropathic pain models. Other studies show that sympathetic blockade may relieve pain in some pain models and clinical conditions. This study examined reduction in peripheral nerve regeneration as one possible mechanism for relief of neuropathic pain by sympathetic blockade. ⋯ In both models, microsympathectomy reduced macrophage density in the sensory ganglia and peripheral nerve. This corroborates previous work showing that sympathetic nerves may locally affect immune function. The results further highlight the challenge of improving pain in neuropathic conditions without inhibiting peripheral nerve regeneration that might otherwise be possible and desired.