The journal of pain : official journal of the American Pain Society
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The present study evaluated the antinociceptive effect of (1→3),(1→6)-linked β-glucan (GL) isolated from Pleurotus pulmonarius (Fr.) Quel. in mice and its possible mechanism of action. Intraperitoneal administration of GL inhibited glutamate-induced licking with an ID(50) of 0.34 mg/kg and inhibition of 96% ± 3%. The treatment of animals with GL (1 mg/kg i.p.) inhibited nociception induced by intrathecal injection of N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate and interleukin -1β in 67% ± 13%, 89% ± 11%, 74% ± 9%, and 75% ± 7%, respectively, but not the nociceptive response induced by (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid, substance P, and tumor necrosis factor-α. Moreover, GL (30 mg/kg i.p.) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 2 hours, with inhibition of 47% ± 10% observed 0.5 hours after treatment. When given chronically (twice a day) over 7 days, GL reversed the mechanical allodynia caused by partial sciatic nerve ligation (inhibition of 45% ± 13% to 60% ± 8%). Interestingly, GL did not affect the locomotor activity of mice in an open field test with doses that produce antinociceptive effects. Our findings show that GL inhibits acute and neuropathic pain in mice through mechanisms that involve the inhibition of ionotropic glutamate receptors and the interleukin -1β pathway. ⋯ This article presents the antinociceptive activity of GL in acute and neuropathic pain with participation of ionotropic glutamate receptors and pro-inflammatory cytokines (interleukin-1β). After further experiments, this compound may represent a new pharmacological agent for the treatment of clinical pain.
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Randomized Controlled Trial Multicenter Study
A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia.
Postherpetic neuralgia (PHN) is a painful complication of acute herpes zoster. This multicenter, double-blind, controlled study randomized 299 PHN patients to receive either NGX-4010, a high-concentration capsaicin (8%) patch, or a low-concentration capsaicin (0.04%) control patch for 30, 60, or 90 minutes. The mean percent reductions in NPRS score from baseline to weeks 2 through 8 were significantly greater in the total NGX-4010 group (26.5%, P = .0286) and the 90-minute NGX-4010 group (27.8%, P = .0438) compared to the pooled control group (17.3%). After review of the data suggested a difference between genders in reporting of pain scores and a higher proportion of males (61%) in the 60-minute NGX-4010 group, post hoc gender-stratified analyses were performed and showed that the 60-minute NGX-4010 group also had a significantly larger mean percent reduction in average pain scores (28.0%, P = .0331). Pain reduction in the 30-minute NGX-4010 group, although similar in magnitude to the other doses, was not significantly different from control in either of these analyses. Similar results were observed during weeks 2 through 12. Most treatment-emergent adverse events were application-site specific, transient and mostly mild to moderate in severity. ⋯ This article reports the safety and efficacy of NGX-4010 applied for 3 different durations (30, 60, or 90 minutes) in patients with PHN. The results identified the 60-minute duration as the dose to be evaluated in subsequent studies and identified a gender effect on reported changes in pain.
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Randomized Controlled Trial Comparative Study
Pain and functioning of rheumatoid arthritis patients based on marital status: is a distressed marriage preferable to no marriage?
Relationships may influence adjustment to chronic pain conditions such as rheumatoid arthritis (RA). We examined how both marital status and marital adjustment were related to pain, physical disability, and psychological disability in 255 adults with RA. Among married participants (n = 158), better marital adjustment (assessed using the Locke-Wallace Marital Adjustment Scale) was correlated with less pain and physical and psychological disability (all P values < .05). Married participants were divided into distressed (n = 44) and nondistressed (n = 114) subgroups and compared with unmarried participants (n = 97). Controlling for demographics and disease severity, unmarried participants had higher affective pain (P = .009) and higher psychological disability (P = .02) than only the nondistressed married participants, but unmarried participants did not differ from distressed married participants. These findings suggest that being married in itself is not associated with better health in RA but that being in a well-adjusted or nondistressed marriage is linked with less pain and better functioning. ⋯ This study examined relationships of marital status and marital adjustment to pain and physical and psychological disability in RA. Findings underscore the importance of considering not only marital status but also degree of marital adjustment in RA and may inform clinical interventions in this population.
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Comparative Study
Acute pain increases phosphorylation of DCLK-long in the Edinger-Westphal nucleus but not in the hypothalamic paraventricular nucleus of the rat.
The doublecortin-like kinase (DCLK) gene is crucially involved in neuronal plasticity and microtubule-guided retrograde transport of signaling molecules. We have explored the possibility that DCLK is involved in pain-induced signaling events in adult male Wistar rats. Our results show that both DCLK-short and DCLK-long splice variants are present in the cell body and proximal dendrites of neurons in stress-related nuclei, ie, the paraventricular nucleus of the hypothalamus (PVN) and the non-preganglionic Edinger-Westphal nucleus (npEW) in the rostroventral periaqueductal grey. We found that DCLK-long but not DCLK-short is phosphorylated in its serine/proline-rich domain. Furthermore, we demonstrate that phosphorylation of DCLK-long in the npEW is increased by acute pain, whereas DCLK-long phosphorylation in the PVN remains unaffected. This is the first report revealing that DCLK isoforms in the PVN and npEW occur in the adult mammalian brain and that pain differentially affects DCLK-long-mediated neuronal plasticity in these 2 stress-sensitive brain centers. ⋯ Pain is a burden for society and the individual, and although the mechanisms underlying pain are relatively well known, its treatment remains difficult and incomplete. Pain stress can lead to diseases like chronic pain and depression. The differential DCLK-phosphorylation in stress-sensitive brain areas is a potential novel therapeutic target in pain research.
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The Critical-Care Pain Observation Tool (CPOT) is a behavioral scale recommended by experts for pain assessment in critically ill patients unable to verbally communicate. The main goal of this study was to determine the relationship between self-reports of pain intensity and the CPOT score, and establish the sensibility and the specificity of the CPOT to different levels of pain intensity in healthy subjects. A total of 18 healthy subjects participated in the study (mean age = 37.8 years). All subjects underwent a 2 minutes noxious cold pressor test (CPT) at 7°C. Verbal pain ratings were obtained with a visual analog scale (0-100) while pain behaviors were videotaped. Afterwards, 2 independent evaluators quantified pain behaviors using the CPOT. Interrater reliability was supported with an ICC of 0.963 (95%CI [0.904-0.986]). A moderate positive correlation between the CPOT scores and self-reports of pain intensity during the CPT was found (r = 0.52, p = 0.028). Such result indicates that subjects reporting high level of pain showed a higher number or more intense pain behaviors. A cut-off score >2.5/8 on the CPOT led to a sensibility of 64% and a specificity of 86%. Results from this pilot study support that an increase of CPOT score is correlated with moderate to high levels of pain intensity and further support the clinical use of the CPOT. ⋯ This article presents the psychometric properties of a behavioral pain scale called the CPOT which was developed to assess pain in critically ill adults unable to self-report. Our results in healthy subjects showed that the CPOT behavioral score is significantly correlated with the self-report of pain intensity and supports its clinical use.