Articles: hyperalgesia.
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We report the case of a 76 year old lady with metastatic breast cancer, who presented to a hospice in severe distress from uncontrolled pain despite an increase in her opioid dose, alongside generalised hypersensitivity and delirium. The clinical presentation suggested opioid-induced hyperalgesia (OIH). After reduction of the opioid dose, our patient significantly improved to the extent she was discharged home a few weeks later. This report aims to increase awareness of OIH, a clinical phenomenon which remains poorly understood and probably under recognised.
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Persistent pain is reported in up to 34% of patients following total knee arthroplasty (TKA) for management of knee osteoarthritis (KOA). Persistent pain in this group is thought to be at least partly reflective of pain sensory hypersensitivity. The objective of this study was to evaluate sensory hypersensitivity, using mechanical and thermal quantitative sensory testing, in patients about to undergo TKA. ⋯ This study suggested that some individuals about to undergo TKA for their advanced KOA demonstrated widespread mechanical sensory hypersensitivity. These findings have potentially important clinical implications regarding perioperative and longer-term pain management in these patients.
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Spinal cord injury (SCI) commonly results not only in motor paralysis but also in the emergence of neuropathic pain (NeuP), both of which can impair the quality of life for patients with SCI. In the clinical field, it is well known that pregabalin, which binds to the voltage-gated calcium channel alpha-2-delta-1 (α2δ-1) subunit has therapeutic effects on NeuP after SCI. A previous study has demonstrated that SCI increased α2δ-1 in the L4-L6 dorsal spinal cord of SCI rats by Western blot analysis and that the increase of α2δ-1 was correlated with tactile allodynia of the hind paw. However, the detailed feature of an increase in α2δ-1 protein in the spinal dorsal horn and the mechanism of pregabalin effect on SCI-induced NeuP have not been fully examined. ⋯ The present study results suggest that an increase of α2δ-1 in the L4 and L5 dorsal horns after thoracic SCI is derived from the increase in the expression in lumbar spinal neurons. This increase may be involved in the development of NeuP in the hind paws and the therapeutic effect of pregabalin on central NeuP after SCI.
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As an indirect approach to relate previously identified sensory phenotypes of patients suffering from peripheral neuropathic pain to underlying mechanisms, we used a published sorting algorithm to estimate the prevalence of denervation, peripheral and central sensitization in 657 healthy subjects undergoing experimental models of nerve block (NB) (compression block and topical lidocaine), primary hyperalgesia (PH) (sunburn and topical capsaicin), or secondary hyperalgesia (intradermal capsaicin and electrical high-frequency stimulation), and in 902 patients suffering from neuropathic pain. Some of the data have been previously published. Randomized split-half analysis verified a good concordance with a priori mechanistic sensory profile assignment in the training (79%, Cohen κ = 0.54, n = 265) and the test set (81%, Cohen κ = 0.56, n = 279). ⋯ Topical menthol was the only model with significant cold hyperalgesia. Sorting of the 902 patients into these mechanistic phenotypes led to a similar distribution as the original heuristic clustering (65% identity, Cohen κ = 0.44), but the denervation phenotype was more frequent than in heuristic clustering. These data suggest that sorting according to human surrogate models may be useful for mechanism-based stratification of neuropathic pain patients for future clinical trials, as encouraged by the European Medicines Agency.
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Adiponectin, a cytokine secreted by adipocytes, plays an important role in regulating glucose and lipid metabolism. However, the role of adiponectin in pain conditions is largely unknown. This study aimed to identify the role and mechanism of adiponectin in nociceptive sensitivity under physiological and pathological states utilising adiponectin knockout (KO) mice. ⋯ Our results show that adiponectin regulates thermal nociceptive sensitivity by inhibiting activation of DRG neurones, spinal microglia, and somatosensory cortical neurones in physiological and neuropathic pain states. This study has relevance for patients with adiponectin disorders, such as obesity and diabetes.