Articles: hyperalgesia.
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Elevated nerve growth factor (NGF) in the contralateral dorsal root ganglion (DRG) mediates mirror-image pain after peripheral nerve injury, but the underlying mechanism remains unclear. Using intrathecal injection of NGF antibodies, we found that NGF is required for the development of intra-DRG synapse-like structures made by neurite sprouts of calcitonin gene-related peptide (CGRP(+)) nociceptors and sympathetic axons onto neurite sprouts of Kv4.3(+) nociceptors. ⋯ Furthermore, neutralizing the neurotransmitter norepinephrine or CGRP in the synapse-like structures by antibodies has similar analgesic effect. Thus, elevated NGF after peripheral nerve injury induces neurite sprouting and the formation of synapse-like structures within the contralateral DRG, leading to the development of chronic mirror-image pain.
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Randomized Controlled Trial
Movement Evoked Pain and Mechanical Hyperalgesia after Intramuscular Injection of Nerve Growth Factor: A Model of Sustained Elbow Pain.
Lateral epicondylalgia presents as lateral elbow pain provoked by upper limb tasks. An experimental model of elbow pain provoked by movement/muscle contraction and maintained over several days is required to better understand the mechanisms underlying sustained elbow pain. This study investigated the time course and pain location induced by nerve growth factor (NGF) injection into a wrist extensor muscle, and whether movement and muscle contraction/stretch provoked pain. ⋯ This article presents a novel experimental human pain model suitable to study the sustained effects of lateral elbow pain on sensorimotor function and to probe the mechanisms underlying persistent musculoskeletal pain.
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Reg Anesth Pain Med · Nov 2015
Pressure Pain Sensitivity in Patients With Suspected Opioid-Induced Hyperalgesia.
This study was designed to test whether a brief quantitative sensory testing assessment could be used to detect hyperalgesia in patients with suspected opioid-induced hyperalgesia (OIH). ⋯ Whereas there were no differences between patients suspected of having OIH and the healthy controls, the finding that higher doses of opioids were associated with more sensitivity suggests that dose might be an important factor in the development of hyperalgesia. In addition, male patients demonstrated a hyperalgesic response after a bolus of fentanyl. Future studies are needed to develop better diagnostics for detecting hyperalgesia in the clinical setting.
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Randomized Controlled Trial
Analgesic and anti-hyperalgesic effects of melatonin in a human inflammatory pain model: a randomized, double-blind, placebo-controlled, three-arm crossover study.
Antinociceptive effects of melatonin have been documented in a wide range of experimental animal models. The aim of this study was to investigate the analgesic, antihyperalgesic, and anti-inflammatory properties of melatonin using a validated burn injury (BI) model in healthy male volunteers. The design was a randomized, double-blind, placebo-controlled, three-arm crossover study. ⋯ While the BI induced large secondary hyperalgesia areas and significantly increased the markers of inflammation, no significant effects of melatonin were observed with respect to primary or secondary outcomes, compared with placebo. The administration of melatonin was not associated with any adverse effects. Melatonin did not demonstrate any analgesic, antihyperalgesic, or anti-inflammatory properties in the BI model.
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Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O) is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR). The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury. ⋯ These preclinical results suggest that N2O is advantageous for long-lasting neuropathic pain relief after sciatic nerve injury compared with other drugs used in humans such as gabapentinoids or NMDAR antagonists. The present preclinical study provides a rationale for developing comparative clinical studies.