The journal of pain : official journal of the American Pain Society
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Although intrathecal (i.t.) administration of the alpha(2)-adrenoceptor agonist clonidine has a pronounced analgesic effect, the clinical use of clonidine is limited by its side effects. Previously, our laboratory has demonstrated that the subcutaneous injection of diluted bee venom (DBV) into an acupoint (termed apipuncture) produces significant analgesic effect in various pain animal models. The present study was designed to examine whether DBV injection into the Zusanli acupoint (ST-36) could enhance lower-dose clonidine-induced analgesic effects without the development of hypotension, bradycardia, or sedation. In the mouse formalin test, DBV injection produced a dramatic leftward shift in the dose-response curve for clonidine-induced analgesia. In a rat neuropathic pain model i.t. clonidine dose dependently suppressed chronic constriction injury (CCI)-induced mechanical allodynia and thermal hyperalgesia, and this clonidine-induced analgesic effect was significantly potentiated by apipuncture pretreatment. DBV apipuncture alone or in combination with a low dose of i.t. clonidine produced an analgesic effect similar to that of the high dose of clonidine, but without significant side effects. The analgesic effect produced by the combination of i.t. clonidine and apipuncture was completely blocked by pretreatment with an alpha(2)-adrenoceptor antagonist. These data show that DBV-apipuncture significantly enhances clonidine-induced analgesia and suggest that a combination of low dose clonidine with acupuncture therapy represents a novel strategy for pain management that could eliminates clonidine's side effects. ⋯ This study demonstrated that intrathecal clonidine-induced analgesia is significantly enhanced when it is combined with chemical acupuncture treatment. The administration of low-dose clonidine in combination with acupuncture produced a potent analgesic effect without significant side effects and thus represents a potential novel strategy for the management of chronic pain.
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Opiates are currently the mainstay for treatment of moderate to severe pain. However, prolonged administration of opiates has been reported to elicit hyperalgesia in animals, and examples of opiate-induced hyperalgesia have been reported in humans as well. Despite the potential clinical significance of such opiate-induced actions, the mechanisms of opiate-induced hypersensitivity remain unknown. The transient receptor potential vanilloid1 (TRPV1) receptor, a molecular sensor of noxious heat, acts as an integrator of multiple forms of noxious stimuli and plays an important role in the development of inflammation-induced hyperalgesia. Because animals treated with opiates show thermal hyperalgesia, we examined the possible role of TRPV1 receptors in the development of morphine-induced hyperalgesia using TRPV1 wild-type (WT) and knock-out (KO) mice and with administration of a TRPV1 antagonist in mice and rats. Administration of morphine by subcutaneous implantation of morphine pellets elicited both thermal and tactile hypersensitivity in TRPV1 WT mice but not in TRPV1 KO mice. Moreover, oral administration of a TRPV1 antagonist reversed both thermal and tactile hypersensitivity induced by sustained morphine administration in mice and rats. Immunohistochemical analyses indicate that sustained morphine administration modestly increases TRPV1 labeling in the dorsal root ganglia. In addition, sustained morphine increased flinching and plasma extravasation after peripheral stimulation with capsaicin, suggesting an increase in TRPV1 receptor function in the periphery in morphine-treated animals. Collectively, our data indicate that the TRPV1 receptor is an essential peripheral mechanism in expression of morphine-induced hyperalgesia. ⋯ Opioid-induced hyperalgesia possibly limits the usefulness of opioids, emphasizing the value of alternative methods of pain control. We demonstrate that TRPV1 channels play an important role in peripheral mechanisms of opioid-induced hyperalgesia. Such information may lead to the discovery of analgesics lacking such adaptations and improving treatment of chronic pain.
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This study evaluated the ability of end-of-day (EOD) ratings to accurately reflect momentary (EMA) ratings on 10 widely used pain and fatigue items. Rheumatology patients (n = 105) completed >or=5 randomly scheduled EMA assessments of each item per day as well as EOD ratings. Correlations were high between EOD and EMA ratings of the 5 pain items (r = .90 to .92) and somewhat lower for the 5 fatigue/energy items (r = .71 to .86). To examine the ability of EOD ratings to represent 1 week of EMA ratings, 7 EOD ratings were averaged and correlated with EMA (r >or= .95 for pain items, r = .88 to .95 for fatigue/energy items). Further, averaging only 3 to 5 EOD ratings achieved very high correlations with 1 week of EMA ratings. Within-subject correlations of EOD with mean daily EMA across 7 days confirmed patients' ability to provide daily ratings that accurately reflect their day-to-day variation in symptom levels. These EOD results were compared to traditional recall ratings collected in the same protocol. It was concluded (1) that EOD ratings were a better representation of EMA than were recall ratings, and (2) that EOD ratings across a reporting period can replace EMA for studies targeting average levels of pain or fatigue. ⋯ This study in chronic pain patients demonstrated that end-of-day ratings of pain are highly accurate representations of average levels of pain experience across a day; ratings of fatigue were somewhat less accurate, though still at a level that would be valid.
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Clinical Trial
Psychologic influence on experimental pain sensitivity and clinical pain intensity for patients with shoulder pain.
Pain-related fear and pain catastrophizing are 2 central psychologic factors in fear-avoidance models. Our previous studies in healthy subjects indicated that pain-related fear, but not pain catastrophizing, was associated with cold pressor pain outcomes. The current study extends previous work by investigating pain-related fear and pain catastrophizing in a group of subjects with shoulder pain, and included concurrent measures of experimental and clinical pain. Fifty nine consecutive subjects seeking operative treatment of shoulder pain were enrolled in this study (24 women, mean age = 50.4, SD = 14.9). Subjects completed validated measures of pain-related fear, pain catastrophizing, and clinical pain intensity and then underwent a cold pressor task to determine experimental pain sensitivity. Multivariate regression models used sex, age, pain-related fear, and pain catastrophizing to predict experimental pain sensitivity and clinical pain intensity. Results indicated that only pain-related fear uniquely contributed to variance in experimental pain sensitivity (beta = -.42, P < .01). In contrast, sex (beta = -.29, P = .02) and pain catastrophizing (beta = .43, P < .01) uniquely contributed to variance in clinical pain intensity. These data provide additional support for application of fear-avoidance models to subjects with shoulder pain. Our results also suggest that pain-related fear and pain catastrophizing may influence different components of the pain experience, providing preliminary support for recent theoretical conceptualizations of the role of pain catastrophizing. ⋯ This study provided additional information on how specific psychological variables potentially influence experimental and clinical pain. In this sample of subjects with shoulder pain, we replicated findings from our previous studies involving healthy subjects, as fear of pain was uniquely associated with experimental pain sensitivity. In contrast, pain catastrophizing emerged as the sole psychological variable related to clinical pain intensity.
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Previous research indicates that exposure to shock decreases thermal pain sensitivity in humans. This hypoalgesia has been attributed to a centrally mediated fear state that activates descending inhibitory pathways. Animal research suggests that distraction alters the activation of these hypoalgesic systems. To determine whether the pain memory alters the activation of hypoalgesic systems in humans, the present study examined whether a post-shock distractor attenuates shock-induced hypoalgesia. If fear-inducing shocks are represented by a limited capacity working memory system, then a distractor should speed the decay of the hypoalgesia. Healthy men were randomly assigned to 1 of 4 groups: shock-distraction, shock-no distraction, no shock-distraction, and no shock-no distraction. Following baseline pain tests, participants in the shock groups were presented with 3 brief shocks. Immediately following shock, an unexpected vibration stimulus was presented to participants in the distraction groups. Both self-report and physiological (SCL, HR) measures indicated that shock exposure resulted in fear, arousal, and decreased pain sensitivity. Consistent with prior animal studies, presentation of a post-shock distractor sped the decay of shock-induced hypoalgesia. Specifically, the distraction group exhibited significantly less shock-induced hypoalgesia compared to the no-distraction group. These findings provide additional evidence for the involvement of memory processes in the activation of descending pain inhibitory pathways. ⋯ This study demonstrated that the presentation of a distracting stimulus immediately following 3 brief shocks attenuated shock-induced hypoalgesia in healthy human subjects. Understanding the impact of post-pain distraction on pain processing may have important clinical implications because it may influence patients' willingness to undergo future painful medical procedures.