Pain
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Local injections of botulinum toxins have been reported to be useful not only for the treatment of peripheral neuropathic pain and migraine but also to cause long-lasting muscle paralysis, a potentially serious side effect. Recently, a botulinum A-based molecule ("BiTox") has been synthesized that retains neuronal silencing capacity without triggering muscle paralysis. In this study, we examined whether BiTox delivered peripherally was able to reduce or prevent the increased nociceptive sensitivity found in animal models of inflammatory, surgical, and neuropathic pain. ⋯ In contrast, Bitox treatment strongly reduced A-nociceptor-mediated secondary mechanical hyperalgesia associated with either complete Freund's adjuvant (CFA)-induced joint inflammation or capsaicin injection and the hypersensitivity associated with spared nerve injury. These results imply that although local release of neuromodulators from C-fibers was inhibited by BiTox injection, C-nociceptive signaling function was not impaired. Taken together with recent clinical data the results suggest that BiTox should be considered for treatment of pain conditions in which A-nociceptors are thought to play a significant role.
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Multicenter Study
The Pain in Neuropathy Study (PiNS): a cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy.
Disabling neuropathic pain (NeuP) is a common sequel of diabetic peripheral neuropathy (DPN). We aimed to characterise the sensory phenotype of patients with and without NeuP, assess screening tools for NeuP, and relate DPN severity to NeuP. The Pain in Neuropathy Study (PiNS) is an observational cross-sectional multicentre study. ⋯ Brush-evoked allodynia was present in only those with NeuP (15%); the paradoxical heat sensation did not discriminate between those with (40%) and without (41.3%) NeuP. The "irritable nociceptor" subgroup could only be applied to a minority of patients (6.3%) with NeuP. This study provides a firm basis to rationalise further phenotyping of painful DPN, for instance, stratification of patients with DPN for analgesic drug trials.
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Ample empirical evidence endorses the role of associative learning in pain-related fear acquisition. Nevertheless, research typically focused on self-reported and psychophysiological measures of fear. Avoidance, which is overt behavior preventing the occurrence of an aversive (painful) stimulus, has been largely neglected so far. ⋯ During acquisition, the Experimental Group reported more pain-related fear and pain-expectancy to T1 vs T2 vs T3 and deviated more from the shortest trajectory than the Yoked Group. During subsequent extinction, avoidance behavior, self-reported fear, and pain-expectancy decreased significantly, but conditioned differences persisted despite the absence of painful stimuli. To conclude, this operant learning task might provide a valid paradigm to study pain-related avoidance behavior in future studies.
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Multicenter Study
Normative data for Aδ contact heat evoked potentials (CHEPs) in adult population: A multicenter study.
There has been a significant increase over recent years in the use of contact heat evoked potentials (CHEPs) for the evaluation of small nerve fiber function. Measuring CHEP amplitude and latency has clinical utility for the diagnosis and assessment of conditions with neuropathic pain. This international multicenter study aimed to provide reference values for CHEPs to stimuli at 5 commonly examined body sites. ⋯ In general, larger CHEP amplitudes were associated with higher evoked pain scores. Females had CHEPs of larger amplitude and shorter latency than males. This substantive data set of normative values will facilitate the clinical use of CHEPs as a rapid, noninvasive, and objective technique for the assessment of patients presenting with neuropathic pain.