The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
Reliability and validity of a brief method to assess nociceptive flexion reflex (NFR) threshold.
The nociceptive flexion reflex (NFR) is a physiological tool to study spinal nociception. However, NFR assessment can take several minutes and expose participants to repeated suprathreshold stimulations. The 4 studies reported here assessed the reliability and validity of a brief method to assess NFR threshold that uses a single ascending series of stimulations (Peak 1 NFR), by comparing it to a well-validated method that uses 3 ascending/descending staircases of stimulations (Staircase NFR). Correlations between the NFR definitions were high, were on par with test-retest correlations of Staircase NFR, and were not affected by participant sex or chronic pain status. Results also indicated the test-retest reliabilities for the 2 definitions were similar. Using larger stimulus increments (4 mAs) to assess Peak 1 NFR tended to result in higher NFR threshold estimates than using the Staircase NFR definition, whereas smaller stimulus increments (2 mAs) tended to result in lower NFR threshold estimates than the Staircase NFR definition. Neither NFR definition was correlated with anxiety, pain catastrophizing, or anxiety sensitivity. In sum, a single ascending series of electrical stimulations results in a reliable and valid estimate of NFR threshold. However, caution may be warranted when comparing NFR thresholds across studies that differ in the ascending stimulus increments. ⋯ This brief method to assess NFR threshold is reliable and valid; therefore, it should be useful to clinical pain researchers interested in quickly assessing inter- and intra-individual differences in spinal nociceptive processes.
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Chronic pain after breast cancer treatment is a major clinical problem, affecting 25 to 60% of patients. Development of chronic pain after breast cancer treatment, as well as other surgical procedures, involves a complex pathophysiology that involves pre-, intra- and post-operative factors. This review is a systematic analysis on methodology and evidence in research into persistent pain after breast cancer treatment during the period 1995 to 2010, in order to clarify the significance and relative role of potential risk factors. Literature was identified by a search in PubMed and OVID, as well as by obtaining relevant studies from a systematic review of reference lists. Sixty papers were identified, most of these being retrospective or questionnaires. Only 2 studies included quantitative sensory testing and only 26 studies were prospective. Furthermore, about a third of the studies did not apply modern principles of surgical and adjuvant therapy. In summary, the data show inconsistencies in definition of chronic pain and treatment groups, as well as in the collection of pre- intra- and post-operative data, precluding conclusions with regard to pathophysiologic mechanisms as well as rational strategies for prevention and treatment. However, nerve damage and radiotherapy appear to be significant risk factors for chronic pain. A proposal for the design of future prospective studies is presented. ⋯ A comprehensive and systematic approach to research in chronic pain after breast cancer treatment is necessary in order to understand the pathophysiology and thus develop strategies for prevention and treatment.
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We have recently developed an animal model of fibromyalgia syndrome in the rat. In this model, rats exposed to unpredictable sound stress develop a delayed onset enhancement and prolongation of cytokine-induced mechanical hyperalgesia in muscle and skin. In this study, we tested the hypothesis that our model also manifests symptoms of common comorbid diagnoses: irritable bowel syndrome, temporomandibular disorder, and anxiety. Both visceral sensitivity and cytokine hyperalgesia in masseter muscle were present in the stressed rats. Furthermore, in an established model of irritable bowel syndrome-water avoidance-we observed significant muscle hyperalgesia. Finally, using the elevated plus maze to assess for anxiety level, we observed a significantly higher anxiety level in sound stress-exposed rats. Thus, unpredictable sound stress produces a condition in the rat with several features-delayed onset visceral and temporomandibular hyperalgesia and increased anxiety, as well as cutaneous and muscle hyperalgesia-commonly found in patients with fibromyalgia syndrome. ⋯ A stress model-unpredictable sound-in the rat exhibits several features (cutaneous, musculoskeletal, and visceral hyperalgesia, as well as anxiety) that are found in patients with fibromyalgia syndrome. Thus, this model may be used to test hypotheses about the underlying mechanisms and response to therapy in patients with fibromyalgia.
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Cold hyperalgesia is 1 of the characteristic signs in neuropathic pain. Topical application of menthol has been proposed as model to study cold hyperalgesia. The aim of this psychophysical study was to characterize the human surrogate of neuropathic pain of topical menthol application by using a standardized and validated protocol of quantitative sensory testing (QST). Additionally, we assessed the course of the signs elicited by menthol application over time. High-concentration 40% L-menthol was applied topically on hairy skin in 12 healthy subjects. Standardized psychophysical tests (QST) assessing 13 parameters including thermal and mechanical detection and pain thresholds were obtained before and every 45 minutes after menthol removal up to 4 hours after menthol application. Menthol decreased the cold pain threshold, mechanical pain threshold, and increased the mechanical pain sensitivity in all subjects displaying cold and mechanical pinprick hyperalgesia. In all subjects, an area of secondary pinprick hyperalgesia could be determined. Within the observation time, the decreased cold pain threshold increased continuously, whereas the signs of primary and secondary pinprick hyperalgesia remained stable. The data suggest that topical 40% menthol application is a useful model for studies of cold hyperalgesia and pinprick hyperalgesia in humans. ⋯ This study establishes the topical application of high-concentration 40% menthol as a useful stable model for studies of cold hyperalgesia and pinprick hyperalgesia in humans. The provided long-term data are important for psychophysical and pharmacological research in humans and provide us with insights on experimental cold and mechanical hyperalgesia.
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Randomized Controlled Trial
Efficacy of low-dose celecoxib in patients with acute pain.
The sore throat pain model was used to evaluate single-dose effects of celecoxib 50 and 100 mg over 6 hours in the treatment of acute pharyngeal pain. Multiple-dose effects of 50-mg bid and 100 mg followed by 50 mg over 6 to 24 hours were also evaluated. Under double-blind, randomized, placebo-controlled conditions, 269 adults with confirmed acute pharyngitis rated throat pain intensity, throat soreness, difficulty swallowing, and sore throat pain relief over 24 hours. For the primary efficacy analysis (SPID2), patients receiving celecoxib 100 mg during the first 2 hours after the first dose had significantly higher mean scores than patients in the placebo group (P < .0003). Efficacy was also demonstrated for celecoxib 50 and 100 mg compared with placebo for all end points (including total pain relief, summed pain intensity differences, total reduction of throat soreness, and difficulty swallowing) at all time points after the first dose and after the second 50-mg dose (P < .01). There were no differences between the dosage regimens, although a supplementary 50-mg dose of celecoxib 6 to 12 hours after the first dose appeared to provide additional efficacy over 24 hours. No serious adverse events (AEs) or discontinuations due to an AE were reported. The results of this study demonstrate that in this pain model, celecoxib is a well tolerated and efficacious analgesic in 50- and 100-mg doses. ⋯ In a double-blind, randomized, placebo-controlled trial utilizing the sore throat pain model, low-dose celecoxib (50- and 100-mg doses) was well tolerated and provided effective analgesia in patients with acute pain.