Articles: hyperalgesia.
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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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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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Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. ⋯ The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia.
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Noxious stimulation at critical stages of development has long-term consequences on somatosensory processing in later life, but it is not known whether this developmental plasticity is restricted to nociceptive pathways. Here, we investigate the effect of repeated neonatal noxious or innocuous hind paw stimulation on adult spinal dorsal horn cutaneous mechanical sensitivity. Neonatal Sprague-Dawley rats of both sexes received 4 unilateral left hind paw needle pricks (NPs, n = 13) or 4 tactile (cotton swab touch) stimuli, per day (TC, n = 11) for the first 7 days of life. ⋯ After incision, injury sensitivity of adult wide-dynamic-range neurons to both noxious and dynamic tactile hypersensitivity was significantly greater in NP animals compared with TC and undisturbed controls. We conclude that both repeated touch and needle-prick stimulation in the neonatal period can alter adult spinal sensory neuron sensitivity to both innocuous and noxious mechanical stimulation. Thus, spinal sensory circuits underlying touch and pain processing are shaped by a range of early-life somatosensory experiences.
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Anesthesia and analgesia · Jun 2018
The Opiorphin Analog STR-324 Decreases Sensory Hypersensitivity in a Rat Model of Neuropathic Pain.
Neuropathic pain represents a therapeutic challenge, and treatments with increased efficacy and tolerability still need to be developed. Opiorphin protects endogenous enkephalins from degradation, potentiating enkephalin-dependent analgesia via the activation of opioid pathways. Enkephalins are natural ligands of opioid receptors, with strong affinity for δ-opioid receptors. Expression of functional δ-opioid receptors increases in sensory neurons after peripheral nerve injury in neuropathic pain models. In a postoperative pain model, opiorphin and its stable analog STR-324 have an analgesic potency comparable to that of morphine, but without adverse opioid-related side effects. Consequently, administration of endogenous opiorphin peptides or STR-324 might be effective in managing peripheral neuropathic pain. ⋯ These observations suggested that STR-324 may be an effective addition to the multimodal approach for treating clinical neuropathic pain.