Articles: hyperalgesia.
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Intramuscular injection of Nerve Growth Factor (NGF) may influence the responsiveness of active chemo-sensitive channels affecting muscle pain sensitivity. This double-blinded crossover study in healthy humans assessed contraction-evoked pain responses and pain sensitivity during acute ischaemia in the tibialis anterior (TA) muscle before and 24 hr after five distributed NGF injections (1 µg, 4 cm interval) compared with control injections (isotonic-saline). ⋯ Acidification of the muscle environment may affect muscle nociceptors and pain by different mechanisms, including activation of ASIC3 and TRPV1. In this study, pain evoked following ischaemic contractions was increased in the Nerve Growth Factor (NGF)-sensitized muscle compared with non-ischaemic contractions and in the non-sensitized muscle. These findings illustrate that responses of peripheral afferents under ischaemic conditions are altered by a pre-sensitized muscle. This highlights the role of growth factors, including NGF, in peripheral muscle sensitization with clinical implications for ischaemic myalgia.
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J. Pharmacol. Exp. Ther. · Nov 2019
Pharmacological Assessment of Sepiapterin Reductase Inhibition on Tactile Response in the Rat.
There is an unmet medical need for nonopioid pain therapies in human populations; several pathways are under investigation for possible therapeutic intervention. Tetrahydrobiopterin (BH4) has received attention recently as a mediator of neuropathic pain. Recent reports have implicated sepiapterin reductase (SPR) in this pain pathway as a regulator of BH4 production. ⋯ SPR inhibition and mechanical allodynia were assessed coordinately with pterin biomarkers in plasma and at the site of neuronal injury (i.e., dorsal root ganglion). Upon daily oral administration for 3 consecutive days, unbound plasma concentrations of test article exceeded the unbound in vivo rat SPR IC90 throughout the dose intervals, leading to a 60% reduction in BH4 in the dorsal root ganglion. Despite evidence for pharmacological modulation of the BH4 pathway, there was no significant effect on the tactile paw withdrawal threshold relative to vehicle-treated controls.
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Randomized Controlled Trial
Short-Term Effects of 10% Lidocaine Ointment on Allodynia in Cancer Pain: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.
Background: There is currently no established therapy for allodynia, which is a type of neuropathic pain. However, high concentrations of topical anesthetics can anesthetize the skin and increase the sensory threshold to tactile stimulation. Objective: We aimed to evaluate the short-term effects and safety of 10% lidocaine ointment for treating allodynia in cancer pain. Design: This was a randomized double-blind crossover study comparing the efficacies of 10% lidocaine ointment and placebo ointment for the treatment of static allodynia and spontaneous pain within 24 hours after ointment application, using a numerical rating scale (NRS). Setting/Subjects: The subjects were 25 cancer patients with current pain rating of ≥4 on NRS of static allodynia in cancer pain. Results: The NRS scores for static allodynia were significantly lower in the lidocaine group than in the placebo group at two to eight hours after initial ointment application. ⋯ There was no interaction between time and group in terms of NRS values for spontaneous pain (p = 0.835), but a significant main effect of group was found, with NRS scores being significantly lower in the lidocaine group than in the placebo group (p = 0.027). There were no adverse events associated with lidocaine use. Conclusions: Lidocaine ointment 10% can alleviate allodynia for two to eight hours after application.
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Advances in the field of pharmacogenomics have resulted in the discovery of some important single-nucleotide polymorphisms which are found to be associated with opioid dose variability. This, to a large extent, explains genetic variability in the analgesic dose of opioids. ⋯ An in-depth knowledge of single-nucleotide polymorphisms can help clinicians to address interindividual variability in opioid dosing and requirements. In the era of precision medicine, these genetic markers can also help us to design prognostic tools to accurately predict the analgesic dose of opioids.
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Exercise is considered an important component of effective chronic pain management and it is well-established that long-term exercise training provides pain relief. In healthy, pain-free populations, a single bout of aerobic or resistance exercise typically leads to exercise-induced hypoalgesia (EIH), a generalized reduction in pain and pain sensitivity that occurs during exercise and for some time afterward. In contrast, EIH is more variable in chronic pain populations and is more frequently impaired; with pain and pain sensitivity decreasing, remaining unchanged or, in some cases, even increasing in response to exercise. ⋯ The clinical implications of impaired EIH are discussed and recommendations are made for future research, including further exploration of individual differences in EIH, the relationship between exercise dose and EIH, the efficacy of combined treatments and the use of alternative measures to quantify EIH. PERSPECTIVE: This article provides a contemporary review of the acute effects of exercise on pain and pain sensitivity, including in people with chronic pain conditions. Existing findings are critically reviewed, clinical implications are discussed, and recommendations are offered for future research.