The journal of pain : official journal of the American Pain Society
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Opioid withdrawal is characterized by a set of physical and psychological symptoms that depend on both opioid and patient specific characteristics. The present study aims to identify different latent classes of chronic pain patients according to the type of opioid withdrawal symptoms experienced, and to analyze the relationships between the classes and demographic, opioid therapy, psychological and substance use variables. This cross-sectional descriptive study included 391 chronic pain patients on long-term opioid therapy. ⋯ PERSPECTIVE: Although interdose opioid withdrawal is common in chronic pain patients, this study shows 3 different patterns in its experience (mild, moderate, and severe withdrawal). A more severe withdrawal may result in reduced effectiveness of opioids in relieving pain and increased negative consequences, such as higher risk of POUD. Findings that could help improve chronic pain management.
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Increasing evidence suggests that migraine may be the result of an impaired brain glucose metabolism. Several studies have reported brain mitochondrial dysfunction, impaired brain glucose metabolism and gray matter volume reduction in specific brain areas of migraineurs. Furthermore, peripheral insulin resistance, a condition demonstrated in several studies, may extend to the brain, leading to brain insulin resistance. ⋯ Lastly, insulin resistance may link migraine with its comorbidities, like obesity, depression, cognitive impairment and cerebrovascular diseases. PERSPECTIVE: Although additional experimental studies are needed to support this novel "neuroenergetic" hypothesis, brain insulin resistance in migraineurs may unravel the pathophysiological mechanisms of the disease, explaining the migraine chronification and connecting migraine with comorbidities. Therefore, this hypothesis could elucidate novel potential approaches for migraine treatment.
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Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to generate SA in the absence of extrinsic depolarizing inputs. ⋯ These findings suggest that conserved physiological mechanisms of SA in human nociceptor somata can drive neuropathic pain despite documented cellular differences between human and rodent DRG neurons. PERSPECTIVE: Electrophysiological alterations in human sensory neurons associated with patient-reported neuropathic pain include all three of the functional alterations that logically can promote spontaneous activity. The similarity of distinctively altered spontaneous depolarizations in human DRG neurons and rodent nociceptors suggests that spontaneously active human nociceptors can persistently promote neuropathic pain in patients.
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The lateral parabrachial nucleus (LPBN) plays an important role in the processing and establishment of pain aversion. It receives direct input from the superficial dorsal horn and forms reciprocal connections with the periaqueductal grey matter (PAG), which is critical for adaptive behaviour and the modulation of pain processing. Here, using in situ hybridization and optogenetics combined with in vitro electrophysiology, we characterized the spinal- and PAG-LPBN circuits of rats. ⋯ These findings may support the efforts to develop pinpointed therapies for pain patients. PERSPECTIVE: The LPBN is an important brain region for the control of pain aversion versus recuperation, and as such constitutes a promising target for developing new strategies for pain management. We show that clinically-relevant drugs have complex and pathway-specific effects on LPBN processing of putative nociceptive and aversive inputs.
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Classic trigeminal neuralgia (CTN) is a neuropathic pain disorder displaying spontaneously stabbing or electric shock-like paroxysms in the face. Previous research suggests structural and functional abnormalities in brain regions related to sensory and cognitive-affective dimensions of pain contribute to the pathophysiology of CTN. However, few studies to date have investigated how changes in whole-brain functional networks and white matter connectivity are related to CTN. ⋯ These results suggest that altered structural and functional connectivity between aIns and ACC may underpin the aberrant SN in patients with CTN and provide an alternative target for clinical interventions. PERSPECTIVE: This article presents distinctive abnormalities of functional and structural connectivity from aIns to ACC in the patients with CTN, which is associated with pain ratings. This measure could potentially provide an alternative target for clinicians to alleviate this type of intermittent and refractory pain.