The journal of pain : official journal of the American Pain Society
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Arthritis is associated with decreases in local pH. Of the acid-sensing ion channels (ASIC), ASIC3 is most sensitive to such a pH change, abundantly expressed in dorsal root ganglion (DRG), and critical for the development of secondary hyperalgesia. The purpose of this study was to investigate the upregulation of ASIC3, using an acute arthritic pain model in mice. We examined ASIC3 expression in DRG neurons innervating the knee joint with and without carrageenan-induced arthritis by means of retrograde labeling and immunohistochemistry. We also examined the difference of DRG phenotype between ASIC3+/+ and ASIC3-/- mice. ASIC3 immunoreactivity was present in 31% of knee joint afferents and dominantly in small cells. After joint inflammation, ASIC3-immunoreactive neurons significantly increased in number by 50%. Calcitonin gene-related peptide (CGRP) increased similarly in both ASIC3+/+ and ASIC3-/- mice. Soma size distribution of ASIC3-immunoreactive neurons without CGRP expression was shifted to smaller-diameter neurons. Our results suggest that ASIC3 plays an important role in acute arthritic pain. Specifically, we propose that ASIC3 upregulation along with CGRP and phenotypic change in ASIC3-immunoreactive neurons without CGRP are responsible for the development of secondary hyperalgesia after carrageenan-induced arthritis. ⋯ This article shows that ASIC3 is upregulated along with CGRP in knee joint afferents and that there is a phenotypic change in ASIC3-immunoreactive nonpeptidergic neurons in an animal model of acute arthritis. Understanding the basic neurobiology after acute arthritis could lead to future new pharmacological management of arthritis.
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The purpose of this study was to evaluate the impact of smoking status after a diagnosis of lung cancer on reported pain levels. We conducted a telephone survey of patients with lung cancer identified from 4 participating sites between September 2004 and July 2006. Patients were asked to rate their usual pain level over the past week on a 0 to 10 rating scale on which 0 was "no pain" and 10 "pain as bad as you can imagine." We operationally defined persistent smokers as patients who reported continuing to smoke after their lung cancer diagnosis. A logistic regression analysis was used to test the hypothesis that persistent smokers report higher usual pain levels than nonsmokers. Overall, 893 patients completed the survey. The majority (76%) was found to have advanced cancer (stages IIIb and IV). The mean age was 63 years (SD = 10). Seventeen percent of the patients studied were categorized as persistent smokers. The mean pain score for the study sample was 3.1 (SD = 2.7) and 41% reported moderate (4 to 6) or severe pain (7 to 10). A greater proportion of persistent smokers reported moderate or severe pain than nonsmokers or former smokers (P < .001). Logistic regression analysis revealed that smoking status was associated with the usual pain even after adjusting for age, perceived health status, and other lung cancer symptoms such as dyspnea, fatigue, and trouble eating. In conclusion, patients who continue to smoke after a diagnosis of lung cancer report higher levels of usual pain than nonsmokers or former smokers. More research is needed to understand the mechanisms that relate nicotine intake to pain and disease progression in late-stage lung cancer. ⋯ This article examines the relationship between pain and persistent smoking in patients with lung cancer. Although more research is needed to understand the mechanisms that relate nicotine intake to pain and disease progression, physicians can promote smoking cessation in patients with lung cancer to improve health and quality of life.
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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.