Articles: hyperalgesia.
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Sickle cell disease (SCD) pain associates with cold temperature and touch. Patients and murine models with SCD have baseline thermal and mechanical pain. In SCD mice, the baseline hypersensitivity is exacerbated by experimental vaso-occlusive crises. ⋯ There were no differences in heat pain sensitivity. The increased cold (P = 0.02) and mechanical (P = 0.0016) pain sensitivity during hospitalization persisted after adjusting for age, sex, hydroxyurea use, opioid consumption, and numeric pain score. Thus, cold and mechanical pain is significantly worse during an acute SCD painful event as compared to baseline health in patients with SCD.
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Sensitization of the transient receptor potential ion channel vanilloid 1 (TRPV1) is critically involved in inflammatory pain. To date, manifold signaling cascades have been shown to converge onto TRPV1 and enhance its sensitization. However, many of them also play a role for nociceptive pain, which limits their utility as targets for therapeutic intervention. ⋯ Alongside, we identify numerous novel and pain state-dependent binding partners of native TRPV1 in dorsal root ganglia. These data represent a unique resource on the dynamics of the TRPV1 interactome and facilitate mechanistic insights into TRPV1 regulation. We propose that inflammation-related differences in the TRPV1 interactome identified here could be exploited to specifically target inflammatory pain in the future.
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Cholinergic systems modulate synaptic transmission across the neuraxis and play an important role in higher brain function including cognition, arousal and nociception. The anterior cingulate cortex (ACC) is a fundamental brain region for nociception and chronic pain, and receives cholinergic projections mainly from basal forebrain. Recently, we found that the activation of muscarinic M1 receptors in the ACC produced antinociceptive behavior in response to mechanical stimulation. ⋯ Additionally, a type A γ-aminobutyric acid (GABAA) receptor agonist injected into the ACC reduced the mechanical hypersensitivity in this injury model. Finally, a GABAA receptor antagonist blocked the reduction of mechanical hypersensitivity by McN-A-343 in the injury model. Collectively, these results suggest that activations of muscarinic M1 receptors in the ACC reduce nerve injury-induced mechanical hypersensitivity through GABAergic transmission via GABAA receptors.
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Spinal cord stimulation (SCS) represents an important neurostimulation therapy for pain. A new ultra-high frequency (10,000 Hz) SCS paradigm has shown improved pain relief without eliciting paresthesia. We aim to determine whether sub-sensory threshold SCS of lower frequencies also can inhibit mechanical hypersensitivity in nerve-injured rats and examine how electric charge delivery of stimulation may affect pain inhibition by different patterns of subthreshold SCS. ⋯ Inhibition of neuropathic mechanical hypersensitivity can be achieved with low-frequency subthreshold SCS by optimizing the electric charge delivery, which may affect the effect of SCS in individual animals.
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Previous reviews have reported that manifestations of pain sensitization may play an important role in the pain experienced by people with knee osteoarthritis. However, it is unknown if manifestations of pain sensitization are common features across other painful knee disorders or if sensitization requires targeted intervention. This review aims to synthesize the published research investigating manifestations of pain sensitization in painful knee disorders and to evaluate if the manifestations of pain sensitization change in response to treatment. ⋯ Our meta-analysis provides evidence of pain sensitization in people with knee osteoarthritis (strong evidence), people with patellofemoral pain (moderate evidence), and postmeniscectomy patients (very limited evidence). However, conflicting evidence exists in patellar tendinopathy. Metaregression indicates that pain is associated with pressure pain thresholds in knee osteoarthritis. In people with knee osteoarthritis and patellofemoral pain, several interventions were found to reduce manifestations of pain sensitization. This review highlights that pain sensitization may be amenable to treatment through exercise therapy, mobilization, and pharmacological and surgical intervention.