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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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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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.
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Comparative Study
Sex differences in thermal pain sensitivity and sympathetic reactivity for two strains of rat.
Human females are more sensitive than males to brief nociceptive stimuli such as heat and cold. However, a more pronounced peripheral vasoconstriction by females than by males during prolonged nociceptive stimulation predicts that females would be more sensitive to prolonged cold but not heat stimulation. We tested this possibility with reflex (lick/guard) and operant escape and preference tests of sensitivity to prolonged stimulation of Long-Evans and Sprague-Dawley rats. Escape responses to cold stimulation revealed a greater sensitivity of females. In contrast, males were more sensitive to nociceptive heat stimulation. An operant preference test of relative sensitivity to cold or heat stimulation confirmed these results. Cold was more aversive than heat for females, but heat was more aversive than cold for males. Recordings of skin temperature during nociceptive heat stimulation were consistent with the results of operant testing. A reduction in skin temperature (peripheral vasoconstriction) during nociceptive stimulation should increase cold sensitivity as observed for females relative to males. Lick/guard testing did not confirm the results of operant testing. Lick/guard (L/G) responding to nociceptive heat stimulation was greater for females than for males. Female escape responses to heat were more variable than males, but L/G responding of males to the same stimulus was more variable than for females. ⋯ A variety of chronic pain conditions are more prevalent for females, and psychological stress (with attendant sympathetic activation) is implicated in development and maintenance of these conditions. Therefore, understanding relationships between gender differences in pain sensitivity and sympathetic activation could shed light on mechanisms for some varieties of chronic pain.
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This study examined the associations between acculturation and orofacial pain and healthcare among Hispanic adults. Understanding the effects of acculturation on Hispanic oral health may improve understanding of oral health disparities in the United States. Data were collected from 911 Hispanic adults reporting tooth pain and painful oral sores who were part of a larger study of South Florida residents conducted using random-digit dialing methodology. The survey was conducted in Spanish or English by bilingual interviewers per the choice of each respondent. Greater use of the Spanish language was associated with disparities in healthcare visits for orofacial pain, not having a usual dentist, having greater pain, increased difficulty eating and sleeping, and more depression. Respondents' and their parents' nativity (families that had been in the United States longer) and those identifying more closely to Hispanic culture were also predictive of several of the outcomes. Gender, financial status, and age, independent of acculturation, were also associated with orofacial pain, accessing health care, and pain-related loss of functioning among Hispanics. The data support the hypothesis that Hispanics with less acculturation are less able to access needed oral health care. This study highlights the need for outreach programs targeting recent Hispanic immigrants focusing on oral health care. ⋯ This study found that lower levels of acculturation, particularly less frequent use of English, were associated with greater oral pain and depression for Hispanics adults. This emphasizes the need to provide Hispanic patients with information in Spanish and the importance of having bilingual materials and staff in dental clinics.