Articles: neuralgia.
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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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In recent years, the disappointing history of translation in pain research has undergone significant scrutiny. The escalation of knowledge and understanding related to presumed pain in neuropathic and inflammatory animal models contrasted with the unsatisfactory record of "bench-to-bedside" translation has raised many questions about the validity and clinical relevance of preclinical models and methods of behavioral assessment. Although many opinions have been expressed one of the overriding concerns and greatest barriers to the widening gap between preclinical research and the development of new interventions has been the underappreciated distinction between pain and nociception. ⋯ Other issues important to the discussion include but are not limited to the predictive validity of preclinical models, and the neglect of gender, age, and comorbidities in the design of preclinical studies. On the clinical side, the lack of sanitization of phenotypes in clinical trials has also contributed to the insufficient success of efforts to translate basic research to the clinic. The current review will discuss these and other issues believed to have contributed to the existing obstacles and challenges facing pain research along with making recommendations for the future.
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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.
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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.
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Oper Neurosurg (Hagerstown) · Jun 2018
A Prospective Analysis of Neuromonitoring for Confirmation of Lead Placement in Dorsal Root Ganglion Stimulation.
Dorsal root ganglion stimulation is a neuromodulation therapy used for chronic neuropathic pain. Typically, patients are awakened intraoperatively to confirm adequate placement. ⋯ This series demonstrates that the proposed neuromonitoring protocol can be used in an asleep patient to assure proper positioning of the dorsal root ganglion electrode in the dorsal foramen by generating somatosensory evoked potential responses in the absence of electromyogram responses.