Pain
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To investigate the influence of chronic nociceptive pain on endogenous pain modulation, the effect of heterotopic noxious conditioning stimulation (HNCS) on perception of various somatosensory modalities was assessed in 15 patients with painful osteoarthritis of the hip. Thirteen patients were re-assessed when pain-free 6-14 months following surgery. Sex- and age matched healthy subjects assessed at similar time intervals served as controls. ⋯ In the second session, pressure pain thresholds increased during the tourniquet test in controls (P < 0.001) and in patients (P < 0.02). In conclusion, no pressure pain modulation was induced by HNCS in patients before surgery, as opposed to controls, suggesting a dysfunction in systems subserving 'diffuse noxious inhibitory controls' (DNIC). Normal pressure pain modulation induced by HNCS was seen when patients were re-assessed in a pain-free state following surgery, indicating that the dysfunction of DNIC had been maintained by chronic nociceptive pain.
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Since evidence points to the involvement of cholecystokinin (CCK) in nociception, we examined the effect of intrathecal CI-988, an antagonist of the CCK-B receptors, on mechanical hyperalgesia and allodynia in normal, mononeuropathic and diabetic rats,. Owing to the anti-opioid activity of CCK, it has been suggested that hyperactivity in the spinal CCK system is responsible for the low sensitivity of neuropathic pain to opioids. We therefore also evaluated the effect of the combination of i.t. ⋯ The combination of CI-988 and morphine showed a superadditive interaction in the diabetic rats only (477 +/- 16 g; cut-off 750 g), in comparison with the antinociceptive effect of each drug. In addition, CI-988 exhibited a weak anti-allodynic effect in mononeuropathic rats, and no anti-allodynic effect in diabetic rats. These results show the CCK-B receptor blockade-mediated antinociceptive effects and reveals the antinociceptive action of morphine in diabetic rats after CCKergic system inhibition.
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The anticonvulsant gabapentin is effective against neuropathic pain, but the primary site(s) and mechanism(s) of action are unknown. In order to explore the relative contribution of spinal versus supra-spinal mechanisms to the antinociceptive effect of gabapentin, this study used two differentially integrated nociceptive tests. We systematically compared the effects of various doses of gabapentin on the paw withdrawal to pressure (PWTP), a spinally coordinated reflex and the vocalization threshold to paw pressure (VTPP), a supra-spinal integrated test in the sciatic nerve constriction rat model of neuropathic pain. ⋯ Gabapentin at 100 mg/kg but not at 30 mg/kg produced motor deficits in animals using the rotarod test. Taken together, our findings suggest that low doses of gabapentin have a preferential action on the more integrated pain-related behaviour in neuropathic rats. The present results confirm that gabapentin may be a useful approach for the clinical management of several aspects of neuropathic pain.
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Chronic pain, lymphoedema, post-irradiation neuropathy and other symptoms are reported in as many as 75% of women following breast cancer treatment. This study examined pain and sensory abnormalities in women following breast cancer surgery. Sensory tests were carried out on operated and contralateral sides in 15 women with spontaneous pain and sensory abnormalities and 11 pain-free women. ⋯ Pinprick-evoked pain was correlated to spontaneous pain but not to flux. Spontaneous pain was not correlated to flux. Sensitization seems to be a feature in breast cancer-operated women with pain, but not in pain-free women.
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Complete or partial spinal section at T(8) has been shown to block tactile allodynia but not thermal hyperalgesia following L(5)/L(6) spinal nerve ligation (SNL), suggesting the supraspinal integration of allodynia in neuropathic pain. In the present study, the possibility of mediation of nerve injury-associated pain through tonic activity of descending nociceptive facilitation arising from the rostroventromedial medulla (RVM) was investigated. Specifically, the actions of brainstem cholecystokinin and the possible importance of sustained afferent input from injured nerve fibers were determined using pharmacological and physiological approaches in rats with SNL. ⋯ These results suggest that changes in supraspinal processing are likely to contribute to the observed poor efficacy of opioids in clinical states of neuropathic pain. These data also indicate that the activation of descending nociceptive facilitatory pathways is important in the maintenance of neuropathic pain, appears to be dependent on CCK release, and may be driven from sustained afferent input from injured nerves to brainstem sites. Collectively, these data support the hypothesis that abnormal tonic activity of descending facilitation mechanisms may underlie chronic pain from peripheral nerve injury.