Articles: pain-threshold.
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Randomized Controlled Trial
The effect of intradermal microdosing of a transient receptor potential cation channel subfamily V member 1 antagonist on heat evoked pain and thermal thresholds in normal and ultraviolet-C exposed skin in healthy volunteers.
Three TRPV1 (Transient Receptor Potential Vanilloid Receptor 1) antagonists were developed for testing in situ in human skin (Sjögren et al., 2016; Sjögren et al., 2018; Sjögren et al., 2018). The first human study using these compounds and capsaicin, was performed to determine the required local antagonist concentrations needed for target engagement (Proof of Mechanism, PoM) (Sjögren et al., 2018). In this paper, the aim was to address a TRPV1 antagonist's ability to inhibit a more complex pain signal and to define translational endpoints that could be used in further drug development, when progressing orally bioavailable TRPV1 antagonists as novel analgesic medications. ⋯ This study validated translational tools to confirm target engagement for TRPV1 antagonists; WDT, HPT and STHP have utility in this respect, after oral administration of a TRPV1 antagonist. This study also proved that TRPV1 antagonists can inhibit a more complex, non-capsaicin dependent thermally induced pain signal.
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Musculoskelet Sci Pract · Oct 2019
Randomized Controlled Trial Comparative StudyNo difference in pressure pain threshold and temporal summation after lumbar spinal manipulation compared to sham: A randomised controlled trial in adults with low back pain.
Changes in quantitative sensory tests have been observed after spinal manipulative therapy (SMT), particularly in pressure pain thresholds (PPT) and temporal summation (TS). However, a recent systematic review comparing SMT to sham found no significant difference in PPT in patients with musculoskeletal pain. The sham-controlled studies were generally low quality, and conclusions about other quantitative sensory tests could not be made. ⋯ Our results suggest that lumbar SMT does not have a short-term hypoalgesic effect, as measured with PPT and TS, when compared to sham manipulation in people with low back pain.
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Randomized Controlled Trial Pragmatic Clinical Trial
Acute alcohol effects on conditioned pain modulation, but not temporal summation of pain.
Although pain reduction after alcohol administration has repeatedly been demonstrated, alcohol effects on advanced and clinically relevant dynamic pain paradigms are still unknown. As such, temporal summation of pain (TSP) and conditioned pain modulation (CPM) indicate mechanisms of endogenous pain modulation and involve certain neurotransmitter systems crucially influenced by alcohol. Our study is the first to investigate acute alcohol effects on TSP and CPM. ⋯ Temporal summation of pain was not affected by alcohol, and alcohol effects on pain threshold were small and limited to the higher dose. Our findings suggest that analgesic alcohol effects might be mainly driven by an enhancement of endogenous pain inhibition. The frequent use of alcohol as self-medication in chronic pain might be motivated by alcohol temporarily restoring deficient CPM, thus leading to pain relief in the short run and alcohol-related problems in the long run.
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Randomized Controlled Trial
Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study.
Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of α2δ subunits of voltage-gated Ca channels, such as pregabalin, have shown efficacy in reducing mechanical sensitivity in animal models of neuropathic pain. In addition, some data suggest that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased sensitivity to pinprick. ⋯ There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, P = 0.23) or worst pain (29.2% vs 16.0%, P = 0.13) from baseline. Post hoc analysis of patients with CIPN caused by oxaliplatin (n = 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, P = 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.
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Randomized Controlled Trial
Cortisol affects pain sensitivity and pain-related emotional learning in experimental visceral but not somatic pain: a randomized controlled study in healthy men and women.
Despite growing interest in the role of stress mediators in pain chronicity, the effects of the stress hormone cortisol on acute pain remain incompletely understood. In a randomized, double-blind, placebo-controlled study with N = 100 healthy volunteers, we tested the effects of oral hydrocortisone (20 mg) in 2 widely used pain models for the visceral and somatic modality. Salivary cortisol was increased in the hydrocortisone group (time × group: P < 0.001). ⋯ Conditioned pain-related fear in response to predictive cues was only observed for the visceral modality (time × modality: P = 0.026), an effect that was significantly reduced by hydrocortisone compared with placebo (time × group: P = 0.028). This is the first psychopharmacological study to support that acutely increased cortisol enhances pain sensitivity and impairs pain-related emotional learning within the visceral, but not the somatic pain modality. Stress-induced visceral hyperalgesia and deficits in emotional pain-related learning could play a role in the pathophysiology of chronic visceral pain.