Pain
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Cannabinoid receptor (CB1) agonists strongly inhibit behavioral responses to acute noxious stimuli, but their effects on behavioral responses in persistent pain states are less clear. Here, we examined the effects of intrathecal (i.t.) administration of a CB1 agonist, WIN55,212-2, on mechanical allodynia (decreased withdrawal threshold) produced by injections of complete Freund's adjuvant (CFA) in the plantar surface of the rat hindpaw. We measured mechanical thresholds with calibrated von Frey filaments before and after CFA and used Fos expression as a marker of the activity of spinal cord neurons during inflammation and in response to a CB1 antagonist. ⋯ In normal animals, the increase was primarily in laminae V-VI and in the ventral horn; in animals with persistent inflammation SR141716A increased the number of Fos neurons in laminae I-II and V-VI. These results demonstrate that WIN55212-2 reverses inflammation-induced allodynia at doses that do not produce analgesia and that SR141716A differentially affects the pattern of Fos expression in the spinal cord, depending on the presence or absence of inflammation. Taken together, these results suggest that the CB1 receptor system is tonically active in the spinal cord under normal conditions and that its activity is increased in response to injury.
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Amitriptyline, a non-selective noradrenaline (NA) and 5-hydroxytryptamine (5-HT) reuptake inhibitor, has recently been demonstrated to produce a peripheral antinociceptive action in an inflammatory (formalin test) and a neuropathic pain model (spinal nerve ligation). In the present study, we determined whether desipramine, a selective NA reuptake inhibitor, and fluoxetine, a selective 5-HT reuptake inhibitor, could produce peripheral antinociceptive actions in these same tests. Effects on paw volume also were determined. ⋯ The increase in paw volume produced by fluoxetine was inhibited by ketanserin (5-HT2 receptor antagonist), mepyramine (histamine H1 receptor antagonist) and phentolamine (alpha-adrenergic receptor antagonist), but not by the other selective 5-HT receptor antagonists tested or caffeine. The pronounced peripheral pain alleviating actions in the absence of marked changes in paw volume produced by desipramine and amitriptyline, but not fluoxetine, in the formalin test and the spinal nerve ligation model suggest that these agents could be developed as cream or gel formulations to recruit a peripheral antinociceptive action in inflammatory and neuropathic pain states. Such a formulation might permit the attainment of higher and more efficacious concentrations in the region of the sensory nerve terminal, with limited systemic side effects.
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Clinical Trial
Gender differences in associations between trauma history and adjustment among chronic pain patients.
This study examines the relationship between a trauma history and emotional functioning in response to a chronic pain condition. We broadened the traditional study of trauma in chronic pain from sexual and physical abuse to include a variety of traumatic events and experiences that occurred not only during childhood, but during adulthood as well. Seventy-three (51% female, 60% lower back) chronic pain patients were administered the Trauma History Questionnaire (Green, B. ⋯ Univariate tests showed that the interaction was significant only for emotional distress variables and not for pain severity and disability. Further, the multivariate effect of Trauma Group and the univariate effects for emotional distress variables were significant only among men. Results indicate that a substantial history of trauma may detrimentally impact a chronic pain patient's ability to manage their pain effectively, particularly among men.
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Patients who develop malignant infiltration of the psoas muscle and the lumbar plexus often experience a severe complex pain syndrome characterised by deep somatic pain, neuropathic pain and psoas spasm. Conventional analgesic regimes may not relieve these symptoms adequately. We describe the use of patient-controlled boluses of local anaesthetic via a psoas sheath catheter in this scenario. The recent availability of portable infusion pumps with the capability to deliver large volume boluses with long lockout times made this intervention possible and allowed the patient to be discharged home with effective relief of pain.
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Withdrawal reflex responses to graded von Frey filaments applied to the plantar surface of the paw were measured before and after bone hole damage in rats with either a dorsal column (DC) lesion or a sham DC lesion. Two methods were employed to produce models of osteotomy; a small hole was drilled through either the (1) tibia or (2) calcaneus (Houghton, A. K., Hewitt, E. and Westlund, K. ⋯ Nocifensive behavior, characterized by a lifting and guarding of the damaged limb, was also observed in animals with a hole through the calcaneus. In contrast, we found that interrupting the dorsal column pathway with a small mid-line lesion (1 week prior to the osteotomy) prevented the development of both the primary and secondary mechanical hyperalgesia and allodynia but not the guarding of the damaged limb. This study provides evidence that axons in the medial part of the dorsal column are involved in the development of mechanical hyperalgesia and allodynia after bone hole injury.