Articles: neuralgia.
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The somatosensory phenotype of Chinese temporomandibular disorders (TMD) patients is not sufficiently studied with the use of contemporary techniques and guidelines. ⋯ Somatosensory abnormalities were commonly detected in Chinese TMD pain patients both within and outside the primary painful region, strongly indicating disturbances in the central processing of somatosensory stimuli. The individual variations in somatosensory abnormalities indicate a possible need for development of individualized TMD pain management.
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Recent studies reported the translocator protein (TSPO) to play critical roles in several kinds of neurological diseases including the inflammatory and neuropathic pain. However, the precise mechanism remains unclear. This study was undertaken to explore the distribution and possible mechanism of spinal TSPO against chronic neuropathic pain (CNP) in a rat model of L5 spinal nerve ligation (SNL). ⋯ Ro5-4864 also attenuated the spinal CXCR2 and p-ERK expressions. These results suggested that early upregulation of TSPO could elicit potent analgesic effects against CNP, which might be partly attributed to the inhibition of CXCL1-CXCR2-dependent astrocyte-to-neuron signaling and central sensitization. TSPO signaling pathway may present a novel strategy for the treatment of CNP.
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Cav3.2 T-type calcium currents in primary afferents are enhanced in various painful pathological conditions, whereas inhibiting Cav3.2 activity or expression offers a strategy for combating the development of pain hypersensitivity. We have shown that Cav3.2 channel surface density is strongly regulated by the ubiquitination machinery and we identified the deubiquitinase USP5 as a Cav3.2 channel interacting protein and regulator of its cell surface expression. We also reported that USP5 is upregulated in chronic pain conditions. Conversely, preventing its binding to the channel in vivo mediates analgesia in inflammatory and neuropathic pain models. ⋯ Our findings reveal a crucial region in the cUBP domain of USP5 that is important for substrate recognition and binding to the III-IV linker of Cav3.2 channels. Targeting the interaction of this region with the Cav3.2 channel can be exploited as the basis for therapeutic intervention into inflammatory and neuropathic pain.
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Previous studies have shown that ulinastatin, an effective inhibitor of the inflammatory response in clinical applications, can attenuate hyperalgesia in rodents. However, the underlying mechanism remains unclear. In the present study, we first examined the change in the calcineurin level, which plays an important role in regulating cytokine release in the nervous system, following lumbar 5 ventral root transection in the rat. ⋯ Importantly, intraperitoneal injection of ulinastatin alleviated the pain behavior and calcineurin downregulation induced by lumbar 5 ventral root transection. Lastly, the cytokine IL-10 was significantly decreased following lumbar 5 ventral root transection, and application of calcineurin (intrathecal) or ulinastatin (intraperitoneal) inhibited the IL-10 downregulation induced by lumbar 5 ventral root transection. These results suggested that ulinastatin, by acting on the CN/IL-10 pathway, might be a novel and effective drug for the treatment of neuropathic pain.
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There is an urgent need to develop and incorporate novel behavioral tests in classically used preclinical pain models. Most rodent studies are based upon stimulus-evoked hindpaw measurements even though chronic pain is usually a day and night experience. Chronic pain is indeed a debilitating condition that influences the sociability and the ability for voluntary tasks, but the relevant behavioral readouts for these aspects are mostly under-represented in the literature. Moreover, we lack standardization in most behavioral paradigms to guarantee reproducibility and ensure adequate discussion between different studies. This concerns not only the combination, application, and duration of particular behavioral tasks but also the effects of different housing conditions implicating social isolation. ⋯ This is the first longitudinal study providing detailed insights into various voluntary behavioral parameters related to pain and highlights the importance of social environment on spontaneous non-evoked behaviors in a mouse model of chronic neuropathy. Our results provide fundamental considerations for future experimental planning and discussion of pain-related behavioral changes.