Pain
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Loss of GABAergic inhibition in pain pathways has been considered to be a key component in the development of chronic pain. In the present study, we intended to examine whether miR-92b-mediated posttranscriptional dysregulation of spinal potassium chloride cotransporter (KCC2) and vesicular γ-aminobutyric acid transporter (VGAT) plays a major role in the development and maintenance of long-term visceral hyperalgesia in neonatal zymosan-treated rats. Neonatal cystitis was induced by transurethral zymosan administration from postnatal (P) days 14 to 16 (protocol 1). ⋯ Intrathecal administration of lentiviral pLSyn-miR-92b-3p sponge (miR-92b-3p inhibitor) upregulated KCC2 and VGAT expression in spinal dorsal horn neurons. In behavioral studies, intrathecal administration of lentiviral miR-92b-3p sponge attenuated an increase in visceromotor responses and referred viscerosomatic hypersensitivity following the induction of cystitis. These findings indicate that miR-92b-3p-mediated posttranscriptional regulation of spinal GABAergic system plays an important role in sensory pathophysiology of zymosan-induced cystitis.
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Randomized Controlled Trial
Is the rationale more important than deception? A randomized controlled trial of openlabel placebo analgesia.
Research on open-label placebos questions whether deception is a necessary characteristic of placebo effects. Yet, comparisons between open-label and deceptive placebos (DPs) are lacking. We therefore assessed effects of open-label placebos and DPs in comparison with no treatment (NT) with a standardized experimental heat pain paradigm in a randomized controlled trial in healthy participants. ⋯ Our findings reveal that placebos with a plausible rationale are more effective than without a rationale. Even more, open-label placebos did not significantly differ in their effects from DPs. Therefore, we question the ubiquitously assumed necessity of concealment in placebo administration.
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Different sensory profiles in diabetic distal symmetrical sensory-motor polyneuropathy (DSPN) may be associated with pain and the responsiveness to analgesia. We aimed to characterize sensory phenotypes of patients with painful and painless diabetic neuropathy and to assess demographic, clinical, metabolic, and electrophysiological parameters related to the presence of neuropathic pain in a large cohort of well-defined DSPN subjects. This observational cross-sectional multi-center cohort study (performed as part of the ncRNAPain EU consortium) of 232 subjects with nonpainful (n = 74) and painful (n = 158) DSPN associated with diabetes mellitus of type 1 and 2 (median age 63 years, range 21-87 years; 92 women) comprised detailed history taking, laboratory tests, neurological examination, quantitative sensory testing, nerve conduction studies, and neuropathy severity scores. ⋯ Neuropathic pain was further linked to female sex and higher cognitive appraisal of pain as assessed by the pain catastrophizing scale (P < 0.001), while parameters related to diabetes showed no influence on neuropathic pain with the exception of laboratory signs of nephropathy. This study confirms the value of comprehensive DSPN phenotyping and underlines the importance of the severity of neuropathy for the presence of pain. Different sensory phenotypes might be useful for stratification of patients with painful DSPN for analgesic treatment and drug trials.
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Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain, however, this is hampered by their side effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side effects. We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. ⋯ Unlike THC, the low dose THC:CBD anti-allodynia was not cannabinoid receptor mediated. These findings demonstrate that CBD synergistically enhances the pain-relieving actions of THC in an animal neuropathic pain model, but has little impact on the THC-induced side effects. This suggests that low dose THC:CBD combination treatment has potential in the treatment of neuropathic pain.
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Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. ⋯ The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.