Articles: function.
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The transient receptor potential ion channel TRPM3 is highly prevalent on nociceptive dorsal root ganglion (DRG) neurons, but its functions in neuronal plasticity of chronic pain remain obscure. In an animal model of nonspecific low back pain (LBP), latent spinal sensitization known as nociceptive priming is induced by nerve growth factor (NGF) injection. Here, we address the TRPM3-associated molecular basis of NGF-induced latent spinal sensitization at presynaptic level by studying TRPM3-mediated calcium transients in DRG neurons. ⋯ TRPM3 activation provokes an outbreak of pulsatile superoxide production (mitoflash) that comes in the form of a surge in frequency being tunable. We suggest that mitoflash pulsations downstream of TRPM3 activation might be an early signaling event initiating pain sensitization. Tuning of mitoflash activity would be a novel bottom-up therapeutic strategy for chronic pain conditions such as LBP and beyond.
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Comment Randomized Controlled Trial
In degenerative meniscal tears, PT was noninferior to arthroscopic partial meniscectomy for knee function at 5 y.
Noorduyn JCA, van de Graaf VA, Willigenburg NW, et al. Effect of physical therapy vs arthroscopic partial meniscectomy in people with degenerative meniscal tears: five-year follow-up of the ESCAPE randomized clinical trial. JAMA Netw Open. 2022;5:e2220394. 35802374.
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Expectancies for pain and pain relief are central to experimental models of placebo analgesia and nocebo hyperalgesia and are a promising target for clinical intervention in patients with chronic pain. Affective states may play an important role in modulating the degree to which expectancies influence pain, broadening the opportunities for intervention targets. However, findings to date have been mixed and mostly limited to laboratory designs. ⋯ Relatedly, higher morning positive affect predicted greater odds of experiencing a match between pain expectancies and pain experience when the expectation was for low, but not high, pain levels (odds ratio = 1.19, confidence interval: 1.01-1.41, P = 0.03). Negative affect, in contrast, did not significantly influence the assimilation of high pain expectancies with high pain experiences. These findings extend previous experimental studies by showing that the association of daily pain expectancies with pain experience varies as a function of affective state.
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The transient receptor potential cation channel subfamily M member-3 (TRPM3) channel is a recently recognized noxious heat sensor that is involved in inflammatory thermal hyperalgesia. To examine its involvement in the development of hyperalgesia in interstitial cystitis/painful bladder syndrome (IC/PBS), rats with cyclophosphamide (CYP)-induced chronic cystitis were used as a model of IC/PBS. Mechanical and thermal hyperalgesia in lower abdominal region overlying the bladder in CYP rats were measured using von Frey filaments and radiant heat, respectively. ⋯ In CYP rats, pretreatment with the TRPM3 antagonist primidone (2 mg/kg, i.p.) significantly alleviated the mechanical and thermal hyperalgesia, bladder submucosal edema, mast cell infiltration, and bladder hyperactivity. Cyclophosphamide-induced cystitis was associated with TRPM3 upregulation at the mRNA, protein, and functional levels in bladder afferent neurons. Our results suggest that upregulation of TRPM3 channels is involved in the development of chronic pain in CYP-induced cystitis, and targeting TRPM3 may be a pharmacological strategy for treating bladder pain in IC/PBS.