The journal of pain : official journal of the American Pain Society
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The aim of this present study was to test the hypothesis that tonic nociceptive stimulation of latent myofascial trigger points (MTPs) may induce a spatially enlarged area of pressure pain hyperalgesia. Painful glutamate (.2 mL, 1M) stimulation of latent MTPs and non-MTPs in the forearm was achieved by an electromyography-guided procedure. Pain intensity (as rated on the visual analog scale [VAS]) and referred pain area following glutamate injections were recorded. Pressure pain threshold (PPT) was measured over 12 points in the forearm muscles and at the mid-point of tibialis anterior muscle before and at .5 hour, 1 hour, and 24 hours after glutamate injections. The results showed that maximal pain intensity, the area under the VAS curve, and referred pain area were significantly higher and larger following glutamate injection into latent MTPs than non-MTPs (all, P < .05). A significantly lower PPT level was detected over time after glutamate injection into latent MTPs at .5 hour (at 4 points), 1 hour (at 7 points), and 24 hours (at 6 points) in the forearm muscles. However, a significantly lower PPT was observed only at 24 hours after glutamate injection into non-MTPs in the forearm muscles (at 4 points, P < .05) when compared to the pre-injection PPT. PPT at the mid-point of the tibialis anterior was significantly decreased at 1 hour only as compared to the pre-injection PPT in both groups (< .05). The results of the present study indicate that nociceptive stimulation of latent MTPs is associated with an early onset of locally enlarged area of mechanical hyperalgesia. ⋯ This study shows that MTPs are associated with an early occurrence of a locally enlarged area of pressure hyperalgesia associated with spreading central sensitization. Inactivation of MTPs may prevent spatial pain propagation.
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Recently, the lexicon of pain was refined into a parsimonious set of words making up the Pain Descriptor System (PDS). The present study investigated the latent structure of the sensory category of the PDS with its 24 descriptors distributed equally across 8 subcategories. A sample of 629 chronic pain patients rated the degree to which each of these words described their pain. It was found that coldness-related words were rarely used and shared high covariance with other descriptors, thus warranting their removal as a subcategory. Confirmatory factor analysis of a previously theorized single higher-order model of 7 latent factors (each with 3 observed variables) resulted in poor fit, x(2)(181) = 377.72, P < .05; comparative fit index (CFI) = .915; root mean square error of approximation (RMSEA) = .04. This model was replaced with a dual higher-order model retaining the same 7 latent factors plus 2 higher-order factors corresponding to deep pain versus superficial pain. This model provided a good representation of the data, x(2)(181) = 301.07, P < .05; CFI = .948; RMSEA = .032. Therefore, descriptors of pain sensation differentiate sensory quality while also reflecting a fundamental dichotomy supported by neurophysiological research. Thus, the lexicon can illuminate pathophysiology, thereby clarifying pain diagnoses. ⋯ Confirmatory factor analysis was performed on pain sensation descriptors used by 629 patients. This supported a hierarchical model with 7 lower-order factors plus 2 higher-order factors corresponding to deep pain versus superficial pain. By reflecting neurophysiology, this lexicon of pain can offer diagnostic clues.
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The use of von Frey filaments, originally developed by Maximilian von Frey, has become the cornerstone for assaying mechanical sensitivity in animal models and is widely used for human assessment. While there are certain limitations associated with their use that make comparisons between studies not straightforward at times, such as stimulus duration and testing frequency, von Frey filaments provide a good measurement of mechanosensation. Here we describe the application of von Frey filaments to testing in animal models, specifically with respect to determining changes in sensory thresholds in a pain state using the Dixon up-down method. In a literature survey, we found that up to 75% of reports using this method analyze the data with parametric statistical analysis and of those that used nonparametric analysis, none took into account that mechanical sensation is perceived on a logarithmic scale (Weber's Law) when calculating efficacy. Here we outline a more rigorous analysis for calculating efficacy and ED(50)'s from von Frey data that incorporates Weber's Law. We show that this analysis makes statistical and biological sense and provide a specific example of how this change affects data analysis that brings results from animal models more in line with clinical observations. ⋯ This focus article argues that analyzing von Frey paw withdrawal threshold data obtained by using the Dixon up-down method without considering Weber's Law is inappropriate. An analysis method that incorporates how mechanical sensation is perceived and how its application brings results from animal models more in line with clinical data is presented.
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Cancer patients often suffer from pain and most will be prescribed μ-opioids. μ-opioids are not satisfactory in treating cancer pain and are associated with multiple debilitating side effects. Recent studies show that μ and δ opioid receptors are separately expressed on IB4 (-) and IB4 (+) neurons, which control thermal and mechanical pain, respectively. In this study we investigated IB4 (+) and IB4 (-) neurons in mechanical and thermal hypersensitivity in an orthotopic mouse oral cancer model. We used a δ opioid receptor agonist and a P2X(3) antagonist to target IB4 (+) neurons and to demonstrate that this subset plays a key role in cancer-induced mechanical allodynia, but not in thermal hyperalgesia. Moreover, selective removal of IB4 (+) neurons using IB4-saporin impacts cancer-induced mechanical but not thermal hypersensitivity. Our results demonstrate that peripherally administered pharmacological agents targeting IB4 (+) neurons, such as a selective δ-opioid receptor agonist or P2X(3) antagonist, might be useful in treating oral cancer pain. ⋯ To clarify the mechanisms of oral cancer pain, we examined the differential role of IB4 (+) and IB4 (-) neurons. Characterization of these 2 subsets of putative nociceptors is important for further development of effective clinical cancer pain relief.
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Several lines of evidence indicate that brain-derived neurotrophic factor (BDNF) plays a key role as a central pronociceptive modulator of pain, acting through postsynaptic TrkB receptors that trigger intracellular signaling cascades leading to central sensitization. The overall aim of this study was to investigate to what extent BDNF could participate in the generation and maintenance of trigeminal neuropathic pain. The results showed that acute intracisternal administration of nanogram doses of BDNF in naïve mice elicited long-lasting, dose-related, cold allodynic responses to topical application of acetone onto vibrissal pad skin. The systemic administration of cyclotraxin-B (CTX-B), a new TrkB receptor antagonist, or propentofylline, an inhibitor of glial activation, was able to either prevent or reverse the effects of intracisternal BDNF on cold nociception. In addition, the blockade of TrkB receptor by CTX-B inhibited the mechanisms that either initiate or maintain cold allodynia in the ipsilateral vibrissal pad skin after unilateral constriction of the infraorbital nerve. These observations raise the possibility that BDNF is capable on its own of conveying many features of the signaling mechanisms that underlie central sensitization caused by nerve constriction. ⋯ Although further studies are necessary to examine in detail the mechanisms underlying the strong anti-allodynic action of CTX-B, this compound may represent an interesting lead for the development of novel therapeutic strategies aimed at preventing and/or suppressing central sensitization associated with neuropathic pain.