Pain
-
The present study examined the antinociceptive effects of gelsemine, the principal alkaloid in Gelsemium sempervirens Ait. A single intrathecal injection of gelsemine produced potent and specific antinociception in formalin-induced tonic pain, bone cancer-induced mechanical allodynia, and spinal nerve ligation-induced painful neuropathy. The antinociception was dose-dependent, with maximal inhibition of 50% to 60% and ED50 values of 0.5 to 0.6 μg. ⋯ Gene ablation of the GlyR α3 subunit (α3 GlyR) but not α1 GlyR, by a 7-day intrathecal injection of small interfering RNA (siRNA) targeting α3 GlyR or α1 GlyR, nearly completely prevented gelsemine-induced antinociception in neuropathic pain. Our results demonstrate that gelsemine produces potent and specific antinociception in chronic pain states without induction of apparent tolerance. The results also suggest that gelsemine produces antinociception by activation of spinal α3 glycine receptors, and support the notion that spinal α3 glycine receptors are a potential therapeutic target molecule for the management of chronic pain.
-
Fibromyalgia is a common, disabling syndrome that includes chronic widespread pain plus diverse additional symptoms. No specific objective abnormalities have been identified, which precludes definitive testing, disease-modifying treatments, and identification of causes. In contrast, small-fiber polyneuropathy (SFPN), despite causing similar symptoms, is definitionally a disease caused by the dysfunction and degeneration of peripheral small-fiber neurons. ⋯ Blood tests from subjects with fibromyalgia and SFPN-diagnostic skin biopsies provided insights into causes. All glucose tolerance tests were normal, but 8 subjects had dysimmune markers, 2 had hepatitis C serologies, and 1 family had apparent genetic causality. These findings suggest that some patients with chronic pain labeled as fibromyalgia have unrecognized SFPN, a distinct disease that can be tested for objectively and sometimes treated definitively.
-
The aim of this study was to assess the function of the thermo-nociceptive system in 25 patients with long-lasting, medium-to-severe refractory complex regional pain syndrome (CRPS)-1 using behavioral (detection rates and reaction times) and electrophysiological (event-related brain potentials) responses to brief (50 milliseconds) and intense (suprathreshold for Aδ-nociceptors) carbon dioxide laser stimuli delivered to the affected and contralateral limbs, and by comparing these responses to the responses obtained in the left and right limbs of age- and sex-matched healthy controls. Compared with healthy controls and compared with the contralateral limb, the detection rate of pricking pain related to the activation of Aδ-fibers was markedly reduced at the affected limb. Furthermore, reaction times were substantially prolonged (>100 milliseconds in 84% of patients and >300milliseconds in 50% of patients). ⋯ Taken together, our results show that in the majority of patients with chronic CRPS-1, thermo-nociceptive pathways are dysfunctional. A number of pathological mechanisms involving the peripheral nervous system and/or the central nervous system could explain our results. However, the primary or secondary nature of these observed changes remains an open question.
-
Review Meta Analysis
Cognitive and affective reassurance and patient outcomes in primary care: A systematic review.
In the context of uncertainty about aetiology and prognosis, good clinical practice commonly recommends both affective (creating rapport, showing empathy) and cognitive reassurance (providing explanations and education) to increase self-management in groups with nonspecific pain conditions. The specific impact of each of these components in reference to patients' outcomes has not been studied. This review aimed to systematically evaluate the evidence from prospective cohorts in primary care that measured patient-practitioner interactions with reference to patient outcomes. ⋯ Cognitive reassurance was associated with higher satisfaction and enablement and reduced concerns directly after the consultations in 8 studies; with improvement in symptoms at follow-up in 7 studies; and with reduced health care utilization in 3 studies. Despite limitations, there is support for the notion that cognitive reassurance is more beneficial than affective reassurance. We present a tentative model based on these findings and propose priorities for future research.