Pain
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This study evaluated prospectively the incidence of neuropathic pain after thoracotomy, described its clinical characteristics, and delineated landmarks for its diagnosis in daily practice. We evaluated clinically painful symptoms and sensory deficits in 54 patients after lateral/posterolateral thoracotomy for broncho-pulmonary carcinoma with standardized surgical and analgesic procedures. At 2months, 49 patients suffered from non malignant thoracic pain, and at 6months 38 patients (loss to follow-up for 7) reported persisting pain. ⋯ Morphine consumption during the early post-operative period (mean 111.3±30.8mg/day) and pain intensity (VAS: mean 5.71±2.1) were significantly higher in patients suffering from neuropathic pain than in other patients with pain (mean 80±21.4mg/day; VAS: mean 3.9±2.4). The clinical picture in most patients with neuropathic pain included electric shocks and severe multimodal hypoesthesia in the sensory area of 5th/6th intercostal nerves. Thus, our results indicate a minimal incidence of chronic post-thoracotomy pain at 70% and that of neuropathic pain at 29%, this latter being clinically suggested by a combination of certain symptoms and reinforced by the DN4 questionnaire when sensory deficit at scar is present.
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Multiple pathological mechanisms at multiple sensory sites may underlie the pain that follows nerve injury. This provides a basis for recommending more than one agent, either sequentially or in combination, for its treatment. According to this premise, new drugs that combine different mechanisms of analgesic action in a single molecule are gaining momentum, such as tapentadol which stimulates mu-opioid receptors (MOR) and acts as a noradrenaline reuptake inhibitor (NRI) in the CNS. ⋯ In particular, we performed a series of in vivo electrophysiological tests in spinal nerve ligated and sham-operated rats to show that systemic tapentadol (1 and 5mg/kg) dose-dependently reduced evoked responses of spinal dorsal horn neurones to a range of peripheral stimuli, including brush, punctate mechanical and thermal stimuli. Furthermore, we showed that spinal application of the selective α(2)-adrenoceptor antagonist atipamezole, or alternatively the mu-opioid receptor antagonist naloxone, produced near complete reversal of tapentadol's inhibitory effects, which suggests not only that the spinal cord is the key site of tapentadol's actions, but also that no pharmacology other than MOR-NRI is involved in its analgesia. Moreover, according to the extent that the antagonists reversed tapentadol's inhibitions in sham and SNL rats, we suggest that there may be a shift from predominant opioid inhibitory mechanisms in control animals, to predominant noradrenergic inhibition in neuropathic animals.
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Migraine headache is one of the most common neurological disorders. The pathological conditions that directly initiate afferent pain signaling are poorly understood. In trigeminal neurons retrogradely labeled from the cranial meninges, we have recorded pH-evoked currents using whole-cell patch-clamp electrophysiology. ⋯ The desensitization time constant of pH 6.0-evoked currents in the majority of dural afferents was less than 500ms which is consistent with that reported for ASIC3 homomeric or heteromeric channels. Finally, application of pH 5.0 synthetic-interstitial fluid to the dura produced significant decreases in facial and hind-paw withdrawal threshold, an effect blocked by amiloride but not TRPV1 antagonists, suggesting that ASIC activation produces migraine-related behavior in vivo. These data provide a cellular mechanism by which decreased pH in the meninges following ischemic or inflammatory events directly excites afferent pain-sensing neurons potentially contributing to migraine headache.
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Diabetic neuropathy is one of the most common complications of diabetes and causes various problems in daily life. Several investigations have noted that many factors in the spinal cord are involved in the symptoms of painful diabetic neuropathy, and there are very few effective therapeutic regimens. In the present study, we sought to elucidate the role of the RhoA/Rho kinase (ROCK) pathway in thermal hyperalgesia in diabetic mice. ⋯ The expression of eNOS and NO metabolite contents in the spinal cord was decreased in diabetic mice, and these changes were normalized by treatment with simvastatin. The present results show that HMG-CoA reductase inhibitors have an inhibitory effect on thermal hyperalgesia in diabetic mice, which is mediated by an increase in NO production through the inhibition of RhoA/ROCK pathways. These results suggest that ROCK inhibitors and HMG-CoA inhibitors may be attractive compounds to relieve the symptoms of painful diabetic neuropathies.