Pain
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Complex Regional Pain Syndrome (CRPS) is a neuropathic disease that presents a continuing challenge in terms of pathophysiology, diagnosis, and treatment. Recent studies of neuropathic pain, in both animals and patients, have established a direct relationship between abnormal thalamic rhythmicity related to Thalamo-cortical Dysrhythmia (TCD) and the occurrence of central pain. Here, this relationship has been examined using magneto-encephalographic (MEG) imaging in CRPS Type I, characterized by the absence of nerve lesions. ⋯ All CRPS I patients demonstrated peaks in power spectrum in the delta (<4Hz) and/or theta (4-9Hz) frequency ranges resulting in a characteristically increased spectral power in those ranges when compared to control subjects. The localization of such abnormal activity, implemented using independent component analysis (ICA) of the sensor data, showed delta and/or theta range activity localized to the somatosensory cortex corresponding to the pain localization, and to orbitofrontal-temporal cortices related to the affective pain perception. Indeed, CRPS Type I patients presented abnormal brain activity typical of TCD, which has both diagnostic value indicating a central origin for this ailment and a potential treatment interest involving pharmacological and electrical stimulation therapies.
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In the past 30years, the study of nociception has relied mostly on thermal stimulation to activate nociceptors selectively. However, thermal stimulation suffers from some important limitations. For this reason, investigators have proposed intra-epidermal electrical stimulation (IES) as an alternative method to activate nociceptors selectively. ⋯ In a second experiment, we applied a nerve pressure block to the superficial radial nerve to induce a temporally dissociated impairment of Abeta-, Adelta- and C-fibre afferents, and thereby determine the fibre populations contributing to the responses elicited by IES. We found that the time course of the blockade of the responses to IES follows closely the time course of the blockade of Adelta-fibres, but not of Abeta-fibres. Taken together, our results provide converging evidence that Adelta-nociceptors can be activated selectively using IES, provided that low intensities of stimulation are used.
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Injection of hypertonic saline into back muscles or ligaments can induce acute low back pain (LBP). However, no study has systematically investigated pain characteristics from these structures. Further, induced muscle pain can change with stretching and contraction, which is problematic for studies into the effect of pain on sensorimotor control. ⋯ Surprisingly, some participants pointed to a location of pain that was 1-2 segments above or below the injected level. The results highlight that injection into the interspinous ligament elicits consistent pain that is not influenced by trunk movements. These findings support the implementation of this experimental ligament pain model in research.
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Ultraviolet (UV) induced cutaneous inflammation is emerging as a model of pain with a novel sensory phenotype. A UVB dose of 1000mJ/cm2 produces a highly significant thermal and mechanical hypersensitivity. Here we examined the properties and mechanisms of such hyperalgesia in rats. ⋯ Notably alteration in mechanical responses of Adelta- and heat-insensitive C-nociceptors were particular to stronger stimuli. Spontaneous activity was not induced by this dose of UVB. We conclude that UVB-induced mechanical hyperalgesia may be explained by a net shift in peripheral nociceptor response properties.
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Hydrogen sulfide (H(2)S) formed from l-cysteine by multiple enzymes including cystathionine-gamma-lyase (CSE) is now considered a gasotransmitter in the mammalian body. Our previous studies have shown that H(2)S activates/sensitizes Ca(v)3.2 T-type Ca(2+) channels, leading to facilitation of somatic and visceral nociception, and that CSE-derived endogenous H(2)S participates in inflammatory pain. Here, we show novel evidence for involvement of the endogenous H(2)S-Ca(v)3.2 pathway in neuropathic pain. ⋯ Finally, silencing of Ca(v)3.2 in DRG by repeated intrathecal administration of Ca(v)3.2-targeting siRNA significantly attenuated the neuropathic hyperalgesia in the L5SNC rat. In conclusion, our data suggest that Ca(v)3.2 T-type Ca(2+) channels in sensory neurons are upregulated and activated/sensitized by CSE-derived endogenous H(2)S after spinal nerve injury, contributing to the maintenance of neuropathic pain. We thus propose that Ca(v)3.2 and CSE could be targets for the development of therapeutic drugs for the treatment of neuropathic pain.