The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
Respiration-induced hypoalgesia: exploration of potential mechanisms.
Slow breathing is used as a means to reduce pain, yet the mechanisms responsible for respiration-induced hypoalgesia are poorly understood. The present study asked 30 healthy participants (M(age) = 21 years, M(education) = 15 years, 80% white non-Hispanic) to breathe at normal, slow (50% normal), and fast (125% normal) rates while constant-intensity, suprathreshold electric stimulations were delivered to the sural nerve to elicit pain and the nociceptive flexion reflex (NFR, a measure of spinal nociception). Stimulations were equally balanced across inhalations and exhalations to determine whether parasympathetic activation during exhalations contributes to hypoalgesia. Respiration rate, heart rate variability (HRV, a measure of parasympathetic activity), heart rate, and subjective arousal were assessed as manipulation checks. Slow breathing reduced pain relative to normal breathing and fast breathing, but NFR was not influenced by breathing. Further, pain and NFR did not differ between exhalations and inhalations, and changes in HRV did not correlate with changes in pain or NFR. Together, these findings suggest that respiration-induced hypoalgesia does not require gating of spinal nociception or changes in parasympathetic activity. ⋯ Slow breathing reduced pain relative to normal and fast breathing. This respiration-induced hypoalgesia does not appear to be due to gating of spinal nociception or changes in parasympathetic activity.
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Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. The magnitude of tolerance to morphine was comparable following 1, 4, or 8 pretreatments. Tolerance to fentanyl also was evident following 4 or 8 microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the 1 exception of no tolerance to acute administration of fentanyl. ⋯ These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly and is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments.
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In the present study, patients with musculoskeletal pain conditions (n = 55) were filmed while performing a lifting task designed to elicit pain behaviors. Patients were asked to perform the lifting task twice, under 2 distinct conditions. In the first condition, patients were asked to rate their pain while lifting a series of weights. In the second condition, patients were asked to estimate the weight of the objects they lifted. The weight estimation condition was conceived as a way to increase the cognitive load associated with the lifting task. The primary purpose of the present study was to examine whether manipulation of cognitive load differentially influenced the expression of pain behaviors in high and low catastrophizers. During the pain rating condition, results indicated that high catastrophizers displayed significantly higher levels of communicative and protective pain behaviors than low catastrophizers. During the weight estimation condition, however, high and low catastrophizers no longer differed in the expression of communicative pain behaviors. These results suggest that increasing cognitive load during a pain-eliciting task may interfere with the expression of communicative pain behaviors in high catastrophizers. The discussion addresses the potential role of automatic and cognitive control processes in the expression of pain behaviors. ⋯ The present study provides new insights into the processes that might underlie the expression of pain behaviors in patients with high levels of catastrophizing. Our findings could have implications for the management of patients presenting with pain conditions, particularly those with high levels of catastrophizing.
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We previously showed evidence for a genetic association of the human leukocyte antigen (HLA) system and complex regional pain syndrome (CRPS) with dystonia. Involvement of the HLA system suggests that CRPS has a genetic component with perturbed regulation of inflammation and neuroplasticity as possible disease mechanisms. However, it is at present unclear whether the observed association with HLA-B62 and HLA-DQ8 in CRPS patients with dystonia also holds true for patients without dystonia. Therefore, we tested the possible association with HLA-B62 and HLA-DQ8 in a clinically homogeneous group of 131 CRPS patients without dystonia. In addition, we investigated the possible association with other alleles of the HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci. We showed an increased prevalence of HLA-DQ8 (molecularly typed as HLA-DQB1*03:02; OR = 1.65 [95% CI 1.12-2.42], P = .014) in CRPS without dystonia, whereas no association was observed for HLA-B62 (molecularly typed as HLA-B*15:01; OR = 1.22 [95% CI .78-1.92], P = .458). Our data suggest that CRPS with and CRPS without dystonia may be genetically different, but overlapping, disease entities because only HLA-DQ8 is associated with both. The findings also indicate that distinct biological pathways may play a role in both CRPS subtypes. ⋯ This study is the first to replicate a specific HLA region conferring genetic risk for the development of CRPS. Moreover, associations of HLA-DQ8 with both CRPS with and CRPS without dystonia, and HLA-B62 only with CRPS with dystonia, suggest that these disease entities may be genetically different, but overlapping.
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A cross-sectional nationwide epidemiological study was performed in a random sample of the Portuguese adult population, aiming to describe the prevalence and impact of chronic pain (CP). The 5,094 participants were selected by random digit dialing, between January 2007 and March 2008, and estimates were adequately weighted for the population. Prevalence of CP was 36.7% (95% confidence interval [CI] [35.3-38.2]), based on the definition of the International Association for the Study of Pain. Recurrent or continuous pain was present in 85% of those with CP, and moderate-to-severe intensity and disability were present in 68 and 35%, respectively. Highest CP prevalence was observed among the elderly, retired, unemployed, and less educated. Highest disability was found in relation with family/home responsibilities, recreational activities, occupation/work, and sleep/rest; 13% reported a diagnosis of depression and 49% reported interference in their job. The main factors associated with disability were sex, pain intensity, and depression or depressive symptoms. CP is highly prevalent, causes high personal and social burden, and affects particularly the most vulnerable subgroups. Portugal, depending on CP definition, could be placed in the lower prevalence group in Europe. Improvement in pain intensity management and special attention to affective components of CP are recommended. ⋯ In this cross-sectional nationwide epidemiological study, we showed that chronic pain is a significant problem that is present in 37% of the Portuguese adult general population, is associated with high personal, family, and social burden, and affects in particular the most vulnerable subgroups of the population.