The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
Reduction of pain-related fear and disability in post-traumatic neck pain: a replicated single-case experimental study of exposure in vivo.
For patients with acute post-traumatic neck pain (PTNP), pain-related fear has been identified as a potential predictor of chronic disability. If such is the case, fear reduction should enhance the prevention of further pain disability and distress after traumatic neck pain disability. However, exposure-based treatments have not been tested in patients with PTNP. Using a replicated single-case crossover phase design with multiple measurements, this study examined whether the validity of a graded exposure in vivo, as compared with usual graded activity, extends to PTNP. Eight patients who reported substantial pain-related fear were included in the study. Daily changes in pain intensity, pain-related fear, pain catastrophizing, and activity goal achievement were assessed. Before and after each intervention, and at 6-month follow-up, standardized questionnaires of pain-related fear and pain disability were administered, and, to quantify daily physical activity level, patients carried an ambulatory activity monitor. The results showed decreasing levels of self-reported pain-related fear, pain intensity, disability, and improvements in physical activity level only when graded exposure in vivo was introduced, and not in the graded activity condition. The results are discussed in the context of the search for customized treatments for PTNP. ⋯ This is the first study showing that the effects of graded exposure in vivo generalize to patients with chronic PTNP reporting elevated levels of pain-related fear. This could help clinicians to customize treatments for PTNP.
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The firing rate of low threshold motor units is decreased in constant force contractions during experimental pain. However, as firing rate is a determinant of force, it is unclear how force is maintained. Increased synergist muscle activity may compensate. This was investigated by evaluation of motor unit firing rate in synergist ankle plantar flexor muscles (triceps surae). Single motor unit action potentials were recorded in medial gastrocnemius and soleus muscles with fine wire electrodes in 10 subjects. Gross muscle activity was estimated from surface electromyographic (EMG) recordings. Bolus injections of 5% hypertonic saline were injected into lateral gastrocnemius to induce pain (low intensity, 0.5 mL; high intensity, 1.5 mL). Subjects gently plantar-flexed the ankle to recruit 1 to 4 motor units and performed 3 20-second contractions to this target before, during, and after pain. Firing rate decreased approximately 12% in synergist heads of triceps surae during pain and recovered after pain. Despite reduced firing rate, root-mean-square surface EMG amplitude did not change. The effect of nociceptor stimulation is not restricted to painful muscles but reduces motor unit firing in synergist muscles. Changes in synergist muscles cannot explain the maintenance of muscle force. Maintenance of surface EMG amplitude suggests recruitment of additional motor units. ⋯ This study showed that activity of synergist muscles can be affected by muscle pain. However, the changes in activity of synergist muscles may not compensate for changes in the painful muscle. This finding provides evidence of more widespread effects of pain on muscle control.
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Neuropeptides released from axons of primary afferent nociceptive neurons are the key elements for the incidence of neurogenic inflammation and their release is associated with dorsal root reflexes (DRRs). However, whether the release is due to the triggering of DRRs and plays a role in inflammation-induced pain still remain to be determined. The present study assessed the role of calcitonin gene-related peptide (CGRP) in sensitization of primary afferent nociceptors induced by activation of transient receptor potential vanilloid-1 (TRPV(1)) after intradermal injection of capsaicin and determined if this release is due to activation of primary afferent neurons antidromically by triggering of DRRs. Under dorsal root intact conditions, primary afferent nociceptive fibers recorded in anesthetized rats could be sensitized by capsaicin injection, as shown by an increase in afferent responses and lowering of the response threshold to mechanical stimuli. After DRRs were removed by dorsal rhizotomy, the capsaicin-evoked sensitization was significantly reduced. In dorsal root intact rats, peripheral pretreatment with a CGRP receptor antagonist could dose-dependently reduce the capsaicin-induced sensitization. Peripheral post-treatment with CGRP could dose-dependently restore the capsaicin-induced sensitization under dorsal rhizotomized conditions. Capsaicin injection evoked increases in numbers of single and double labeled TRPV(1) and CGRP neurons in ipsilateral dorsal root ganglia (DRG). After dorsal rhizotomy, these evoked expressions were significantly inhibited. ⋯ These data indicate that the DRR-mediated neurogenic inflammation enhances sensitization of primary afferent nociceptors induced by capsaicin injection. The underlying mechanism involves antidromic activation of DRG neurons via upregulation of TRPV(1) receptors whereby CGRP is released peripherally.
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An upregulation of the endogenous opioid, dynorphin A, in the spinal cord is seen in multiple experimental models of chronic pain. Recent findings implicate a direct excitatory action of dynorphin A at bradykinin receptors to promote hyperalgesia in nerve injured rats, and its upregulation may promote, rather than counteract, enhanced nociceptive input due to injury. Here we examined a model of inflammatory pain by unilateral injection of complete Freund's adjuvant (CFA) into the rat hind paw. Rats exhibited tactile hypersensitivity and thermal hyperalgesia in the inflamed paw by 6 hours after CFA injection, whereas a significant elevation of prodynorphin transcripts in the lumbar spinal cord was seen at day 3 but not at 6 hours. Thermal hyperalgesia at day 3, but not at 6 hours, after CFA injection was blocked by intrathecal administration of anti-dynorphin antiserum or by bradykinin receptor antagonists. The antihyperalgesic effect of the latter was not due to de novo production of bradykinin or upregulation of spinal bradykinin receptors. These data suggest that elevated spinal dynorphin on peripheral inflammation mediates chronic inflammatory hyperalgesia. The antihyperalgesic effect of bradykinin receptor antagonists requires the presence of upregulated spinal dynorphin but not of de novo production of bradykinin, supporting our hypothesis that pathological levels of dynorphin may activate spinal bradykinin receptors to mediate inflammatory hyperalgesia. ⋯ This study shows that chronic peripheral inflammation induces a significant upregulation of the endogenous opioid peptide dynorphin. Elevated levels of spinal dynorphin and activation of spinal bradykinin receptors are essential to maintain inflammatory hyperalgesia. The results suggest that blockade of spinal bradykinin receptors may have therapeutic potential in chronic inflammatory pain.
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In recent years, the National Institutes of Health (NIH) has experienced unprecedented reductions in its customary annual budget increases. Consequently, researchers, health care policy planners and others have a pressing need for accurate information on NIH funding patterns. We created a unique and objective system for compiling, classifying, and analyzing data on NIH grant awards and funding for research on pain, nausea, and dyspnea using naïve observers, cross-validation by multiple raters, and face validation by experts. We present results of our method and analyses for the period from 2003 to 2007. Following a 12% increase from 2003 to 2004, funding for pain research fell by 9.4% per year on average over the next 3 years. The percent of the total NIH budget going to support pain research increased to 0.78% in 2004 but fell to 0.61% in 2007. A piecewise regression model confirmed the declining trend represented a significant fit to the data (R(2)=0.98, p=0.024). Separate breakdowns by Institutes showed similar patterns. Analyses of nausea and dyspnea research support revealed small but steady increases over the same period. Declining support for pain research disproportionate to decreases in the NIH budget signals a need for measures to promote funding for meritorious applications. ⋯ Results of 5 year trends in numbers of grants and funding for research in pain, nausea, and dyspnea by the NIH show overall declines for pain but slight increases for nausea and dyspnea. Declining support for pain research that exceeds the reductions in the total NIH budget signals a need for measures to increase pain research funding.