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http://dx.doi.org/10.1093/pm/pnad039 | DOI Listing |
Neuron
September 2025
Shanghai Stomatological Hospital & School of Stomatology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China. Electronic address:
Existing treatments for chronic pain often prove ineffective and carry adverse side effects, highlighting the need for better analgesics, including non-pharmacological treatments. We demonstrate that transcutaneous electrical nerve stimulation (TENS), when repeatedly applied during the early phase of nerve injury in mice, produces sustained analgesic effects by activating the dorsal column nucleus (DCN)-thalamic-cortical pathway, which transmits vibration, discriminative touch, and proprioception. Mechanistically, TENS selectively activates glutamatergic neurons in the DCN (DCN) via exciting Aβ low-threshold mechanoreceptors (Aβ-LTMRs) in dorsal root ganglia (DRGs).
View Article and Find Full Text PDFCureus
September 2025
Rheumatology, University Hospitals Coventry & Warwickshire, Coventry, GBR.
Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that may develop after fractures, surgery, or soft tissue trauma. It is characterized by pain disproportionate to the initial injury, often accompanied by sensory, motor, autonomic, and trophic changes. Despite extensive research, pathophysiology remains unclear, and treatment approaches are varied, with inconsistent supporting evidence.
View Article and Find Full Text PDFSci Signal
September 2025
Center for Neuroscience and Pain Research, Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Opioids relieve pain by activating μ-opioid receptors (MORs), which inhibit communication between pain-sensing neurons (nociceptors) and the spinal cord. However, prolonged opioid use can paradoxically lead to increased pain sensitivity (hyperalgesia) and reduced analgesic efficacy (tolerance), partly because of the activation of NMDA-type glutamate receptors (NMDARs) at the central terminals of primary sensory neurons in the spinal cord. Here, we identified a critical role for the G protein Gα in this paradox.
View Article and Find Full Text PDFJ Neural Transm (Vienna)
August 2025
Core Center for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Neuropathic pain following traumatic nerve injury is a disabling chronic pain disorder characterized by sensory abnormalities such as mechanical allodynia. Botulinum neurotoxin type A (BoNT/A) has shown analgesic properties in a range of clinical pain conditions and in animal models. Here, we investigated analgesic efficacy of recombinant BoNT/A1 (rBoNT/A1; IPN10260) in the spared nerve injury (SNI) mouse model of neuropathic pain.
View Article and Find Full Text PDFJ Neurosci
August 2025
Centre for Neuroscience, Indian Institute of Science, Bengaluru, Karnataka, India - 560012
Acute restraint stress causes analgesia in humans and laboratory animals, but the underlying mechanisms are unknown. Recently, we have shown that a multi-nodal circuitry between the dorsal lateral septum (dLS), lateral hypothalamic area (LHA), and rostral ventromedial medulla (RVM) plays an instructive role in restraint stress-induced analgesia (SIA). We found that the LS neurons are activated when mice struggle to escape the restraint, and we wondered about the origin of the escape signals.
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