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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Mayo Clinic proceedings · Nov 2022
Randomized Controlled TrialClinician Adoption of an Artificial Intelligence Algorithm to Detect Left Ventricular Systolic Dysfunction in Primary Care.
To compare the clinicians' characteristics of "high adopters" and "low adopters" of an artificial intelligence (AI)-enabled electrocardiogram (ECG) algorithm that alerted for possible low left ventricular ejection fraction (EF) and the subsequent effectiveness of detecting patients with low EF. ⋯ Clinicians who most frequently followed the recommendations of an AI tool were twice as likely to diagnose low EF. Those clinicians with less complex patients were more likely to be high adopters.
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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.
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Pain and related consequences could contribute to comorbid illness and premature mortality in homeless and precariously housed persons. We analyzed longitudinal data from an ongoing naturalistic prospective study of a community-based sample (n = 370) to characterize risk factors and consequences of bodily pain. The aims were to describe bodily pain and associations with symptoms and psychosocial function, investigate factors that may increase or ameliorate pain, and examine the consequences of pain for symptoms, functioning, and all-cause mortality. ⋯ The frequency of prescribed and nonprescribed opioid use had nonlinear relationships with pain: intermittent use was associated with severe pain, without reverse association or change with the overdose epidemic. Greater longitudinal mean pain severity was associated with premature mortality, poorer functioning, and suicidal ideation. Considering the relationships between pain, intermittent opioid use, and depressive symptoms could improve health care for precariously housed patients.