An active pronociceptive process involving N-methyl-D-aspartate (NMDA) receptor activation is initiated by opioid administration, leading to opioid-induced pain sensitivity. Experimental observations in rats have reported reduction of baseline nociceptive threshold after prolonged spinal opioid administration. In this study we sought to determine whether a single dose of intrathecal morphine can induce hyperalgesia in uninjured rats and to assess the effects of pretreatment with the NMDA-antagonist ketamine on nociceptive thresholds. Sensitivity to nociceptive stimuli (paw pressure test) was assessed for several days after an acute intrathecal injection of morphine (5 microg and 10 microg) in male Sprague-Dawley rats. The effects of subcutaneously administered NMDA-receptor antagonist ketamine (10 mg/kg) before intrathecally administered morphine were also evaluated. A single intrathecal injection of morphine led to a biphasic effect on nociception; early analgesia associated with an increase in the nociceptive threshold lasting 3-5 h was followed by delayed hyperalgesia associated with a decrease in the nociceptive threshold lasting 1-2 days. Subcutaneous ketamine did not significantly modify the early analgesic component but almost completely prevented the delayed decrease in nociceptive threshold after intrathecal administration of morphine. A single intrathecal injection of morphine in rats produces a delayed and sustained hyperalgesia linked to the development of opioid-induced pain sensitivity.
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http://dx.doi.org/10.1213/01.ANE.0000184136.08194.9B | DOI Listing |
Eur J Pain
March 2025
Department of Life Sciences, South Kensington, Imperial College London, London, UK.
Background: Healthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a 'pro-nociceptive profile' cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti-nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation.
View Article and Find Full Text PDFBrain Sci
January 2025
Center for Experimental Biology, Laboratory of Neuroimmunobiology of Pain, Federal University of Alfenas, Alfenas 37133-840, MG, Brazil.
Background: Chronic postoperative pain (CPOP) is among the main consequences of surgical procedures, directly affecting the quality of life. Although many strategies have been used to treat this symptom, they are often ineffective. Thus, studies investigating CPOP-associated mechanisms may help to develop more effective treatment strategies.
View Article and Find Full Text PDFJ Gen Physiol
March 2025
Institute for Neurophysiology, Uniklinik RWTH Aachen University, Aachen, Germany.
Voltage-gated sodium channels (VGSCs) in the peripheral nervous system shape action potentials (APs) and thereby support the detection of sensory stimuli. Most of the nine mammalian VGSC subtypes are expressed in nociceptors, but predominantly, three are linked to several human pain syndromes: while Nav1.7 is suggested to be a (sub-)threshold channel, Nav1.
View Article and Find Full Text PDFBMC Musculoskelet Disord
January 2025
Department of Physical Medicine, Rheumatology and Rehabilitation, faculty of medicine, Suez Canal University, Ismailia, 41522, Egypt.
Background: Our understanding of osteoarthritis (OA) has evolved from a degenerative disease to one in which low-grade, chronic inflammation plays a central role. In addition, evidence suggests that OA is accompanied by both peripheral and central nervous system sensitization that can cause pain. It has been demonstrated that transcutaneous vagus nerve stimulation (tVNS) can relieve pain, inflammation, and central sensitization in other conditions including fibromyalgia, pelvic pain, and headaches.
View Article and Find Full Text PDFNeurosci Biobehav Rev
January 2025
Department of Psychiatry, University of Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada; Cundill Centre for Child and Youth Depression, Toronto, ON, Canada.
Psychiatric conditions can affect the experience of pain. Several reports indicate that Major Depressive Disorder (MDD) is associated with an increased pain threshold, while Anxiety Disorders (ADs) may amplify the perception of pain. However, available data on the nociceptive threshold in these psychiatric conditions are controversial.
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