The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial Multicenter Study
Treatment of patients with complex regional pain syndrome type I with mannitol: a prospective, randomized, placebo-controlled, double-blinded study.
To assess the effects of intravenous administration of the free radical scavenger mannitol 10% on complaints associated with complex regional pain syndrome Type I (CRPS I), a randomized, placebo-controlled, double-blinded trial was performed. Forty-one CRPS I patients according to the Bruehl et al diagnostic criteria, were included in 2 outpatient pain clinics of 2 university medical centers and randomly assigned to receive either 10% mannitol iv in 1 L 0.9% NaCL in 4 hours for 5 consecutive days or equal volumes of 0.9% NaCL (placebo). Patients in both groups received physical therapy according to protocol and rescue pain medication if required. Complaints on impairment and disability level and quality of life were assessed up to 9 weeks after baseline, with primary measurement points at 2, 6, and 9 weeks. Monitoring of pain using the visual analogue scale took place continuously during the course of the trial. Except for a significant improvement on a subscale of the Jebsen-Taylor hand function test, no significant differences were found between mannitol and placebo treatment. Changes in both groups in the course of the trial were small and clinically irrelevant on all measurement indices. We conclude that intravenous administration of 10% mannitol is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS I. Whether 10% mannitol can provide beneficial effects for subgroups of CRPS I patients with a pathophysiological profile more closely fitting the presumed mode of action for this intervention remains to be established. ⋯ This article addresses the efficacy of the intravenous administration of the free radical scavenger mannitol for treatment of CRPS type 1. This intervention is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS I.
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Randomized Controlled Trial
Massage reduces pain perception and hyperalgesia in experimental muscle pain: a randomized, controlled trial.
Massage is a common conservative intervention used to treat myalgia. Although subjective reports have supported the premise that massage decreases pain, few studies have systematically investigated the dose response characteristics of massage relative to a control group. The purpose of this study was to perform a double-blinded, randomized controlled trial of the effects of massage on mechanical hyperalgesia (pressure pain thresholds, PPT) and perceived pain using delayed onset muscle soreness (DOMS) as an endogenous model of myalgia. Participants were randomly assigned to a no-treatment control, superficial touch, or deep-tissue massage group. Eccentric wrist extension exercises were performed at visit 1 to induce DOMS 48 hours later at visit 2. Pain, assessed using visual analog scales (VAS), and PPTs were measured at baseline, after exercise, before treatment, and after treatment. Deep massage decreased pain (48.4% DOMS reversal) during muscle stretch. Mechanical hyperalgesia was reduced (27.5% reversal) after both the deep massage and superficial touch groups relative to control (increased hyperalgesia by 38.4%). Resting pain did not vary between treatment groups. ⋯ This randomized, controlled trial suggests that massage is capable of reducing myalgia symptoms by approximately 25% to 50%, varying with assessment technique. Thus, potential analgesia may depend on the pain assessment used. This information may assist clinicians in determining conservative treatment options for patients with myalgia.
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Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in mu-opioid receptor (MOR)-G protein coupling from G(i/o) to G(s) that can be prevented by cotreatment with an ultra-low-dose opioid antagonist. In this study, using lumbar spinal cord tissue from rats with L(5)/L(6) spinal nerve ligation (SNL), we demonstrated that SNL injury induces MOR linkage to G(s) in the damaged (ipsilateral) spinal dorsal horn. This MOR-G(s) coupling occurred without changing G(i/o) coupling levels and without changing the expression of MOR or Galpha proteins. Repeated administration of oxycodone alone or in combination with ultra-low-dose naltrexone (NTX) was assessed on the SNL-induced MOR-G(s) coupling as well as on neuropathic pain behavior. Repeated spinal oxycodone exacerbated the SNL-induced MOR-G(s) coupling, whereas ultra-low-dose NTX cotreatment slightly but significantly attenuated this G(s) coupling. Either spinal or oral administration of oxycodone plus ultra-low-dose NTX markedly enhanced the reductions in allodynia and thermal hyperalgesia produced by oxycodone alone and minimized tolerance to these effects. The MOR-G(s) coupling observed in response to SNL may in part contribute to the excitatory neurotransmission in spinal dorsal horn in neuropathic pain states. The antihyperalgesic and antiallodynic effects of oxycodone plus ultra-low-dose NTX (Oxytrex, Pain Therapeutics, Inc., San Mateo, CA) suggest a promising new treatment for neuropathic pain. ⋯ The current study investigates whether Oxytrex (oxycodone with an ultra-low dose of naltrexone) alleviates mechanical and thermal hypersensitivities in an animal model of neuropathic pain over a period of 7 days, given locally or systemically. In this report, we first describe an injury-induced shift in mu-opioid receptor coupling from G(i/o) to G(s), suggesting why a mu-opioid agonist may have reduced efficacy in the nerve-injured state. These data present a novel approach to neuropathic pain therapy.
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Meta Analysis
Acupuncture for tension-type headache: a meta-analysis of randomized, controlled trials.
We investigated the efficacy and safety of acupuncture for the treatment of tension-type headache by conducting a systematic review and meta-analysis of randomized, controlled trials. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from inception through August 2007. No search or language restrictions were applied. Eight randomized, controlled trials met our inclusion criteria. Pooled data from 5 studies were used for the meta-analysis. Our primary outcome was headache days per month. We assessed data from 2 time points: During treatment and at long-term follow-up (20-25 weeks). The weighted mean difference (WMD) between acupuncture and sham groups was used to determine effect size, and a validated scale was used to assess the methodological quality of included studies. During treatment, the acupuncture group averaged 8.95 headache days per month compared with 10.5 in the sham group (WMD, -2.93 [95% CI, -7.49 to 1.64]; 5 trials). At long-term follow-up, the acupuncture group reported an average of 8.21 headache days per month compared with 9.54 in the sham group (WMD, -1.83[95% CI, -3.01 to -0.64]; 4 trials). The most common adverse events reported were bruising, headache exacerbation, and dizziness. ⋯ This meta-analysis suggests that acupuncture compared with sham for tension-type headache has limited efficacy for the reduction of headache frequency. There exists a lack of standardization of acupuncture point selection and treatment course among randomized, controlled trials. More research is needed to investigate the treatment of specific tension-type headache subtypes.
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Randomized Controlled Trial
Ethnic differences in diffuse noxious inhibitory controls.
Substantial evidence indicates that the experience of both clinical and experimental pain differs among ethnic groups. Specifically, African Americans generally report higher levels of clinical pain and greater sensitivity to experimentally induced pain; however, little research has examined the origins of these differences. Differences in central pain-inhibitory mechanisms may contribute to this disparity. Diffuse noxious inhibitory controls (DNIC), or counterirritation, is a phenomenon thought to reflect descending inhibition of pain signals. The current study assessed DNIC in 57 healthy young adults from 2 different ethnic groups: African Americans and non-Hispanic whites. Repeated assessments of the nociceptive flexion reflex (NFR) as well as ratings of electrical pain were obtained before, during, and after an ischemic arm pain procedure (as well as a sham procedure). The DNIC condition (ie, ischemic arm pain) produced substantial reductions in pain ratings as well as electrophysiologic measures of the NFR for all participants when compared with the sham condition (P < .001). The DNIC condition produced significantly greater reductions in verbal pain ratings among non-Hispanic whites when compared with African Americans (P = .02), whereas ethnic groups showed comparable reductions in NFR. The findings of this study suggest differences in endogenous pain inhibition between African Americans and non-Hispanic whites and that additional research to determine the mechanisms underlying these effects is warranted. ⋯ This study adds to the growing literature examining ethnic differences in experimental pain perception. Our data suggest that these variations may be influenced by differences in descending inhibition.