Pain
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The rostral ventromedial medulla (RVM) is critical for the modulation of dorsal horn nociceptive transmission. Three classes of RVM neurons (ON, OFF, and NEUTRAL) have been described that have distinct responses to noxious stimuli and mu opioid receptor (MOR) agonists. The present study in barbiturate anesthetized rats investigated the effects of the delta 2 opioid receptor (DOR2) agonist, [D-Ala2]deltorphin II (DELT), microinfused into the RVM on the tail flick reflex and activity of RVM neurons. ⋯ The activity of NEUTRAL cells was not affected. The antinociceptive effects and corresponding changes in ON and OFF cell activity produced by DELT were antagonized by the DOR2 antagonist, naltriben methanesulfonate, administered at the same site. These DOR2 mediated effects on noxious stimulation-evoked changes in RVM neuronal activity are similar to those reported for MOR agonists and suggest that both DOR2 and MOR produce analgesia through activation of OFF cells.
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We tested the ability of lithium (Li(+)) to block heat hyperalgesia, cold allodynia, mechanical allodynia and mechanical hyperalgesia in rats experimentally subjected to painful peripheral neuropathy. Chronic constrictive injury (CCI) to the sciatic nerve induced persistent hyperalgesia and allodynia. Intrathecal injection of Li(+) (2.5-40 micromol) into the region of lumbar enlargement dose-dependently reduced heat hyperalgesia, cold allodynia and mechanical allodynia for 2-6 h after injection, but had no effect on mechanical hyperalgesia. ⋯ Intrathecal injection of myo-inositol (2.5 mg) significantly reversed both the anti-hyperalgesic and anti-allodynic effect of Li(+). These findings suggest that intrathecal Li(+) suppresses neuropathic pain response in CCI rats through the intracellular phosphatidylinositol (PI) second messenger system in spinal cord neurons. Lithium (Li(+)) has already found widespread clinical application; these results suggest that its therapeutic utility may be extended to include treatment of neuropathic pain syndromes resulting from peripheral nerve injury.