minocycline and tetrapentylammonium

The central amygdaloid nucleus (CeA) is involved in processing and descending regulation of pain. Amygdaloid mechanisms underlying pain processing and control are poorly known. Here we tested the hypothesis that perioperative CeA administration of tetrapentylammonium (TPA), a non-selective THIK-1 channel blocker and thereby inhibitor of microglia, attenuates development of chronic neuropathic pain and comorbid anxiety-like behavior.. Rats with a spared nerve injury (SNI) model of neuropathy or sham operation had a chronic cannula for drug microinjections into the CeA or a control injection site. Monofilament test was used to evaluate pain, and light-dark box (LDB) to assess anxiety.. Perioperative CeA treatment with TPA (30 μg/day up to the third postoperative day, D3) significantly attenuated the development of pain and anxiety-like behavior. In the late phase (> D14), CeA administration of TPA (3-30 μg) failed to influence pain. Perioperative minocycline (microglia inhibitor; 25 μg), MK-801 (an N-Methyl-D-aspartate receptor antagonist; 0.1 μg), vehicle or TPA in a control injection site failed to attenuate pain development.. Perioperative treatment of the CeA with TPA delayed development of neuropathic pain and comorbid anxiety-like behavior, while TPA treatment failed to influence maintenance of established neuropathic pain. The failures to attenuate pain development with CeA administrations of minocycline or MK-801 do not support the hypothesis that the TPA-induced prophylactic effect was due to inhibition of amygdaloid microglia or N-methyl-D-aspartate receptors. While TPA in the CeA proved to have a prophylactic effect on SNI-induced pain behavior, the underlying mechanism still remains to be studied.

Topics: Amygdala; Analgesics; Animals; Anti-Anxiety Agents; Anxiety; Behavior, Animal; Disease Models, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Locomotion; Male; Microglia; Microinjections; Minocycline; Neuralgia; Pain Perception; Pain Threshold; Peripheral Nerve Injuries; Potassium Channels, Tandem Pore Domain; Quaternary Ammonium Compounds; Rats, Wistar; Receptors, N-Methyl-D-Aspartate