Pain
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Observational Study
Cannabis use disorder in chronic pain patients: over- and underestimation in a cross-sectional observational study in three German pain management centres.
There are concerns that cannabis use disorder (CUD) may develop in patients with chronic pain prescribed medical cannabis (MC). The criteria for CUD according to the Statistical Manual for Mental Disorders Version 5 (DSM-5) were not developed for the identification of patients using cannabis for therapeutic reasons. In addition, some items of CUD might be attributed to the desire of the patient to relieve the pain. ⋯ Urine tests were positive for nonprescribed drugs (amphetamines and tranquilizer) in 4.8% of subjects. Physicians identified abuse in 1 patient. In this study, the DSM-5 criteria overestimated and physicians underestimated the prevalence of CUD in patients prescribed MC for chronic pain.
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Transient voltage-gated sodium currents are essential for the initiation and conduction of action potentials in neurons and cardiomyocytes. The amplitude and duration of sodium currents are tuned by intracellular fibroblast growth factor homologous factors (FHFs/iFGFs) that associate with the cytoplasmic tails of voltage-gated sodium channels (Na v s), and genetic ablation of Fhf genes disturbs neurological and cardiac functions. ⋯ Here, we use electrophysiological and computational methods to show that the heat nociception deficit can be explained by the combined effects of elevated temperature and FHF2 deficiency on the fast inactivation gating of Na v 1.7 and tetrodotoxin-resistant sodium channels expressed in dorsal root ganglion C fibers. Hence, neurological and cardiac heat-associated deficits in Fhf2null mice derive from shared impacts of FHF deficiency and temperature towards Na v inactivation gating kinetics in distinct tissues.
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Although pain dysfunction is increasingly observed in Huntington disease, the underlying mechanisms still unknown. As a crucial Huntington-associated protein, Huntington-associated protein 1 (HAP1) is enriched in normal spinal dorsal horn and dorsal root ganglia (DRG) which are regarded as "primary sensory center," indicating its potential functions in pain process. Here, we discovered that HAP1 level was greatly increased in the dorsal horn and DRG under acute and chronic pain conditions. ⋯ Furthermore, SNI-induced activation of astrocytes and microglia notably decreased in HAP1-deficient mice. These results indicate that HAP1 deficiency might attenuate pain responses. Collectively, our results suggest that HAP1 in dorsal horn and DRG neurons regulates Cav1.2 surface expression, which in turn reduces neuronal excitability, BDNF secretion, and inflammatory responses and ultimately influences neuropathic pain progression.
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Neuronal N-type (Ca V 2.2) voltage-gated calcium channels are essential for neurotransmission from primary afferent terminals in the dorsal horn. In this study, we have used a knockin mouse containing Ca V 2.2 with an inserted extracellular hemagglutinin tag (Ca V 2.2_HA), to visualise the pattern of expression of endogenous Ca V 2.2 in dorsal root ganglion (DRG) neurons and their primary afferents in the dorsal horn. We examined the effect of partial sciatic nerve ligation (PSNL) and found an increase in Ca V 2.2_HA only in large and medium dorsal root ganglion neurons and also in deep dorsal horn synaptic terminals. ⋯ We also found that following PSNL, there is patchy loss of glomerular synapses immunoreactive for Ca V 2.2_HA and CGRP or IB4, restricted to the superficial layers of the dorsal horn. This reduction is not dependent on α 2 δ-1 and likely reflects partial deafferentation of C-nociceptor presynaptic terminals. Therefore, in this pain model, we can distinguish 2 different events affecting specific DRG terminals, with opposite consequences for Ca V 2.2_HA expression and function in the dorsal horn.
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A multisystem phenotype with the Triad of bodily pain, psychological distress, and sleep disturbance was found to have high risk for developing initial onset of painful temporomandibular disorders (TMDs) in the multicenter Orofacial Pain: Prospective Evaluation and Risk Assessment dataset. In this study, we systemically examined phenotypic characteristics and explored potential pathophysiology in quantitative sensory testing and autonomic nervous system domains in this multisystem Triad phenotype. Secondary analysis was performed on 1199 non-Triad and 154 Triad TMD-free Orofacial Pain: Prospective Evaluation and Risk Assessment enrollees at baseline. ⋯ These findings highlight the importance of whole-person multisystem assessment at the stage before developing complex pain conditions, such as TMDs, and suggest that, in addition to a "tissue damage monitor," pain should be considered in a broader context, such as a component within a "distress monitoring system" at the whole-person level when multisystem issues copresent. Therefore, the presence or absence of multisystem issues may carry critical information when searching for disease mechanisms and developing mechanism-based intervention and prevention strategies for TMDs and related pain conditions. Cardiovascular autonomic function should be further researched when multisystem issues copresent before developing TMDs.