Pain
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This study evaluated the effects of spinal gamma-aminobutyric acid (GABA) receptor agonists on the tactile allodynia observed in rats with ligation of the L5/L6 nerve roots (Chung model) and chronic lumbar intrathecal catheters. In these rats, the spinal injection of the GABAB agonist baclofen (BAC; 0.03-03 micrograms) and GABAA agonist muscimol (MUS; 0.1-1.0 micrograms) resulted in a dose-dependent antagonism of the allodynia at doses which had no detectable effect upon motor function. ⋯ The antagonistic effects were limited to the agonist of the respective receptor. These observations indicate that spinal GABAA and GABAB receptors modulate spinal systems activated by low threshold mechanoreceptors which mediate the allodynia observed following peripheral nerve injury.
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Randomized Controlled Trial Clinical Trial
Pharmacokinetics and pharmacodynamics of twenty-four-hourly Kapanol compared to twelve-hourly MS Contin in the treatment of severe cancer pain.
Twenty-four patients with severe pain related to cancer completed a randomised, double-blind, double-dummy, crossover study examining morphine pharmacokinetics and pharmacodynamics when the same 24-h morphine dose was administered using two modified release oral morphine formulations; either one dose of Kapanol (a new sustained release polymer coated pellet formulation administered in capsule form, Glaxo Wellcome group of companies) per 24 h, or MS Contin (Purdue Frederick Company, Connecticut, USA) administered at 12-h intervals. The morphine dose was optimised for each patient using an immediate release morphine solution in the lead-in period to provide the most favourable balance between pain relief and side-effects. Patients were then randomly allocated to receive their 24-h morphine dose as either Kapanol or MS Contin in period 1. ⋯ Some of these pharmacokinetic differences (e.g., Cmin and fluctuation in plasma morphine concentration) were surprising given that the dosing interval for Kapanol (24 h) was double that of MS Contin (12 h). There was no significant difference between the Kapanol and MS Contin treatment phases in any of the pharmacodynamic parameters, morphine related side-effects, the percentage of patients taking rescue medication as well as the amount or time to the first dose of rescue analgesia on day 7 in periods 1 and 2, patient or investigator assessments of global efficacy at the end of periods 1 and 2, or patient treatment preference at the end of the study. Once a day Kapanol provided the same degree of pain relief and morphine related side-effects as 12-h MS Contin.
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Duration of acute herpetic pain (AHP) in 1431 patients for whom treatment was begun within 14 days after the onset of herpes zoster (HZ) was analyzed with respect to age, involved region, and severity of skin lesions. All patients were treated with repeated sympathetic nerve blocks until their pain was almost nil. Severity of the skin lesions at the worst phase was defined as mild when they covered less than one-quarter of the primary dermatome, as severe when they covered more than three-quarters of the primary dermatome, and moderate if they were between mild and severe. ⋯ Multiple stepwise regression analysis revealed that the most important factors influencing the duration of AHP were the severity of skin lesions of HZ at the worst phase (r = 0.412), age (r = 0.277) and the involved region (r = -0.101). Thus, AHP in the elderly and in cases of trigeminal involvement is longer because of higher frequencies of severe HZ in the elderly and in trigeminal involvement rather than "being aged' and "trigeminal involvement' itself. We propose that one needs to analyze the results of treatment of AHP with respect to the severity of skin lesions at the worst phase.
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Two studies that assess fear and avoidance in patients with chronic pain are presented. In the first study, 200 patients with chronic back pain were classified, using the Multidimensional Pain Inventory (Kerns et al., 1985) clustering procedure, as dysfunctional (n = 53), interpersonally distressed (n = 37), and adaptive copers (n = 62). Groups were compared on common measures of anxiety, fear and avoidance. ⋯ In the second study, pain-specific fear and avoidance measures were used in a discriminant function analysis to predict the MPI classification of an independent sample of 55 patients with chronic pain. The measures correctly classified 76.5% of the dysfunctional group and 71.1% of a composite group of interpersonally distressed and adaptive copers. The implications of these findings are discussed.
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Neuropathic pains arising from peripheral nerve injury can result in increased sensitivity to both noxious and non-noxious stimuli and are accompanied by a number of neuroplastic alterations at the level of the spinal cord including upregulation of neurotransmitters including dynorphin, cholecystokinin and neuropeptide Y. Additionally, such pain states appear to be associated with activation of excitatory amino acid receptors including the N-methyl-D-aspartate (NMDA) receptor. Neuropathic pains have often been classified as 'opioid resistant' in both clinical and laboratory settings. ⋯ Co-administration, however, of i.t. morphine with MK-801, or i.t. antisera to dynorphin A (1-13) given prior to morphine elicited both a full antiallodynic response and a complete block of the tail-flick reflex in nerve-injured animals. These results suggest that tonic activation of NMDA receptors, following peripheral nerve injury, is involved with the attenuation of the effectiveness of spinal morphine in a model of neuropathic pain. Additionally, this tonic NMDA activity may be mediated, in part, by increased levels of endogenous dynorphin associated with peripheral nerve injury.