Pain
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Randomized Controlled Trial Comparative Study Clinical Trial
Addition of ultralow dose naloxone to postoperative morphine PCA: unchanged analgesia and opioid requirement but decreased incidence of opioid side effects.
Ultralow doses of naloxone (0.001-0.1 microg/kg) produce analgesia in animal models. However, no clinical study has evaluated the combination of ultralow dose naloxone and morphine using patient-controlled analgesia (PCA). This randomized, double blind controlled study sought to determine if the combination of ultralow dose naloxone and morphine in PCA solutions affects opioid requirements, analgesia, and side effects. ⋯ The morphine+naloxone group had a lower incidence of nausea and pruritus than the morphine group (P=0.01 for both symptoms). However, the incidence of vomiting, time to tolerate fluids, sedation, and urinary retention were similar between groups (all P values >0.1). The combination of ultralow dose naloxone and morphine in PCA does not affect analgesia or opioid requirements, but it decreases the incidence of nausea and pruritus.
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Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre-menopausal women. Previous quantitative sensory test (QST) studies have demonstrated reduced vestibular pain thresholds in these patients. Here we try to find whether QST findings correlate to disease severity. ⋯ This test had the highest kappa value (0.82), predicting correctly 88% of all VVS cases and 100% of the severe VVS cases. Supra-threshold pain magnitude estimation for tonic heat stimulation also had a high kappa value (0.73) predicting correctly 82% overall with a 100% correct diagnosis of the control group. QST techniques, both threshold and supra-threshold measurements, seem to be capable of discriminating level of severity of this clinical pain syndrome.
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Comparative Study
Novel mechanism of enhanced nociception in a model of AIDS therapy-induced painful peripheral neuropathy in the rat.
To elucidate the underlying mechanisms involved in AIDS therapy-induced peripheral neuropathy, we have developed a model of nucleoside analog reverse transcriptase inhibitor-induced painful peripheral neuropathy in the rat, using 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyinosine (ddI) and 2',3'-didehydro-3'-deoxythymidine (d4T), AIDS chemotherapeutic drugs that are also components of AIDS highly active anti-retroviral therapy. Administration of ddC, ddI and d4T produced dose-dependent mechanical hypersensitivity and allodynia. Peripheral administration of inhibitors of protein kinase A, protein kinase C, protein kinase G, p42/p44-mitogen-activated protein kinase (ERK1/2) and nitric oxide synthase, which have demonstrated anti-hyperalgesic effects in other models of metabolic and toxic painful peripheral neuropathies, had no effect on ddC-, ddI- and d4T-induced hypersensitivity. ⋯ Intradermal or spinal injection of intracellular calcium modulators (TMB-8 and Quin-2), which had no effect on nociception in control rats, significantly attenuated and together eliminated ddC and suramin-induced mechanical hypersensitivity. In electrophysiology experiments in ddC-treated rats, C-fibers demonstrated alterations in pattern of firing as indicated by changes in the distribution of interspike intervals to sustained suprathreshold stimuli without change in mechanical activation thresholds or in number of action potentials in response to threshold and suprathreshold stimulation. This study provides evidence for a novel, calcium-dependent, mechanism for neuropathic pain in a model of AIDS therapy-induced painful peripheral neuropathy.
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Comparative Study
Cholinergic modulation of nociceptive responses in vivo and neuropeptide release in vitro at the level of the primary sensory neuron.
Muscarinic acetylcholine receptors (mAChRs) have been widely reported as pharmacological targets for the treatment of pain. However, most of these efforts have focused on CNS mAChRs and their role in modulating nociception at the level of the spinal cord. The present study examines the contribution of peripheral mAChRs in trigeminal nociceptive pathways using a combination of in vivo and in vitro approaches. ⋯ Finally, combined in situ hybridization/immunofluorescence demonstrated that m2 mRNA was present in 20% of trigeminal ganglion neurons between 30 and 60 microm in diameter and that 5-9% of these also expressed CGRP or VR1 immunoreactivity. These results show that activation of peripheral M2 receptors produces antinociception in vivo and the inhibition of nociceptor activity in vitro. While histological analyses at the level of the trigeminal neuronal cell bodies leave open the question of whether the effects of M2 agonists are direct or indirect, these data indicate that primary sensory neuronal M2 receptors may represent a viable peripheral target for the treatment of pain and inflammation.
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Chronic pain and depression are two of the most common health problems that health professionals encounter, yet only a handful of epidemiological studies have investigated the relationship between these conditions in the general population. In the present study we examined the prevalence and correlates of major depression in persons with chronic back pain using data from the first cycle of Canadian Community Health Survey in a sample of 118,533 household residents. The prevalence of chronic back pain was estimated at 9% of persons 12 years and older. ⋯ The rate of major depression increased in a linear fashion with greater pain severity. In logistic regression models, back pain emerged as the strongest predictor of major depression after adjusting for possible confounding factors such as demographics and medical co-morbidity. The combination of chronic back pain and major depression was associated with greater disability than either condition alone, although pain severity was found to be the strongest overall predictor of disability.