Pain
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Controlled Clinical Trial
Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy.
This study aims to individualize the selection of drugs for neuropathic pain by examining the potential coupling of a given drug's mechanism of action with the patient's pain modulation pattern. The latter is assessed by the conditioned pain modulation (CPM) and temporal summation (TS) protocols. We hypothesized that patients with a malfunctioning pain modulation pattern, such as less efficient CPM, would benefit more from drugs augmenting descending inhibitory pain control than would patients with a normal modulation pattern of efficient CPM. ⋯ No predictive role was found for TS. In conclusion, the coupling of CPM and duloxetine efficacy highlights the importance of pain pathophysiology in the clinical decision-making process. This evaluative approach promotes personalized pain therapy.
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Serotonin is critically involved in neuropathic pain. However, its role is far from being understood owing to the number of cellular targets and receptor subtypes involved. In a rat model of neuropathic pain evoked by chronic constriction injury (CCI) of the sciatic nerve, we studied the role of 5-HT(2B) receptor in dorsal root ganglia (DRG) and the sciatic nerve. ⋯ In the latter structure, it was biphasic, consisting of a transient early increase (23-fold), 2 days after the surgery and before the neuropathic pain emergence, followed by a steady (5-fold) increase, that remained constant until pain disappeared. In DRG and sciatic nerve, 5-HT(2B) receptors were immunolocalized on sensory neurons and infiltrating macrophages. Our data reveal a relationship between serotonin, immunocytes, and neuropathic pain development, and demonstrate a critical role of 5-HT(2B) receptors in blood-derived macrophages.