Pain
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Randomized Controlled Trial Comparative Study Clinical Trial
Intravenous dextromethorphan to human volunteers: relationship between pharmacokinetics and anti-hyperalgesic effect.
The aim of this study was to investigate the effect of dextromethorphan (DM) 0.5 mg/kg administered intravenously (i.v.) on hyperalgesia and pain after a tissue injury in human volunteers, and to describe the relationship between pharmacokinetic and pharmacodynamic data. The heat-capsaicin sensitisation model, a well-established experimental hyperalgesia model was induced in 24 healthy, male volunteers aged 21-35 years. The subjects received i.v. ⋯ The pharmacokinetic-pharmacodynamic relationship showed a large inter-subject variation with a mean delay in effect of nearly 2 h in relation to peak serum concentration. The results strongly indicate that DM is an anti-hyperalgesic drug. The delay in effect may be explained by several mechanisms and suggests that timing of DM administration is an essential factor for using the drug in clinical settings.
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Comparative Study
Chronic spinal pain and physical-mental comorbidity in the United States: results from the national comorbidity survey replication.
This paper investigates comorbidity between chronic back and neck pain and other physical and mental disorders in the US population, and assesses the contributions of chronic spinal pain and comorbid conditions to role disability. A probability sample of US adults (n=5692) was interviewed. Chronic spinal pain, other chronic pain conditions and selected chronic physical conditions were ascertained by self-report. ⋯ However, comorbid conditions explained about one-third of the gross association of chronic spinal pain with role disability. We conclude that chronic spinal pain is highly comorbid with other pain conditions, chronic diseases, and mental disorders, and that comorbidity plays a significant role in role disability associated with chronic spinal pain. The societal burdens of chronic spinal pain need to be understood and managed within the context of comorbid conditions.
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Some electrophysiologic studies demonstrate new, excitatory alpha2-adrenoceptors on peripheral nociceptors and their dorsal root ganglion (DRG) cell bodies after nerve injury, yet administration of alpha2-adrenoceptor agonists at these sites reduces hypersensitivity rather than worsens it. Since TRPV-1 expressing nociceptor afferents are important in many pain states, we examined the expression of this channel and its co-expression with alpha2C-adrenoceptors in injured DRG cell bodies and the ability of alpha2-adrenoceptors to inhibit responses to stimulation. Rats underwent tight ligation of the left L5 and L6 spinal nerves, followed by behavioral testing, removal of L5 and L6 DRGs, and either immunostaining for TRPV-1 channels and alpha2C-adrenoceptors or intracellular calcium videomicroscopy in response to electrical field stimulation before and after perfusion with clonidine and capsaicin. ⋯ The proportion of clonidine inhibited cells which responded to capsaicin increased 5 fold after injury. We conclude that TRPV-1 and alpha2C-adrenoceptors are up-regulated in some injured medium and large size neurons after nerve ligation. Increased co-expression by immunocytochemistry, and increased proportion of cells inhibited by clonidine and expressing functional TRPV-1 channels suggest that these cells may play an important role in the analgesic effects of alpha2-adrenoceptor agonists in neuropathic pain.
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Comparative Study
Intrathecal morphine and ketorolac analgesia after surgery: comparison of spontaneous and elicited responses in rats.
Pain after surgery results in significant morbidity, and systemic opioids often fail to provide adequate analgesia without marked sedation and respiratory depression. Intrathecal morphine provides better analgesia, but is limited by delayed respiratory depression. Intrathecal injection of the cyclooxygenase inhibitor, ketorolac, has recently entered clinical trials, and the current study examined the interaction between intrathecal morphine and ketorolac to treat postoperative pain. ⋯ These data confirm that spinal opioid receptor and cyclooxygenase enzyme inhibition diminish elicited tactile hypersensitivity after surgery, and that they similarly return spontaneous behavior to normal. Differences in drug potency could reflect fundamental differences in outcome measures or in the surgical procedures themselves. These data support combination study of intrathecal morphine and ketorolac for postoperative pain.
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Randomized Controlled Trial Comparative Study Clinical Trial
Rofecoxib attenuates both primary and secondary inflammatory hyperalgesia: a randomized, double blinded, placebo controlled crossover trial in the UV-B pain model.
The analysis of drug's influence on peripheral and central sensitisation can give useful information about its mode of action and can lead to more efficacy in the treatment of pain. Peripheral inflammation is associated with peripheral expression and up-regulation of cyclooxygenase 2 (COX-2) in the CNS. The relative contribution of COX-2 mediated central sensitisation may be prominent under inflammatory conditions. ⋯ No significant difference between the three dosage groups was observed. These data confirm peripheral effects of rofecoxib in a human inflammatory UV-B pain model and provide circumstantial evidence that even a standard clinical dose of rofecoxib reduces central hyperalgesia in inflammatory pain. We confirm that the effect of single oral dose of rofecoxib plateaus at 50 mg.