Histaminergic involvement in neuropathic pain produced by partial ligation of the sciatic nerve in rats.
OBJECTIVE
Because the histaminergic system in the brain is involved in regulation of pain, the relationship between central histaminergic activity and neuropathic pain is of interest.


METHODS
Neuropathic pain was induced in rats by partial ligation of the left sciatic nerve, and changes in the extracellular concentration of histamine in the right striatum were examined by a microdialysis procedure 2 weeks later. The nociceptive threshold was determined with von Frey tests, and effects of histaminergic ligands were examined.


RESULTS
Although the extracellular concentration of histamine did not differ between the sham-operated and ligated groups, histaminergic activity assessed by metoprine-induced accumulation of histamine was facilitated in ligated animals. The metoprine treatment ameliorated neuropathic pain in ligated animals, although the agent did not affect the threshold in sham-operated rats. Either intracerebroventricular (ICV) administration of histamine (30 microg) or intraperitoneal (IP) administration of L-histidine (370 mg/kg) decreased the nociceptive threshold in ligated rats. However, a high dose of histamine (180 microg ICV) increased the nociceptive threshold. Ranitidine (100 microg ICV), an H2 antagonist, increased the threshold, whereas pyrilamine (15 microg ICV), an H1 antagonist, showed no remarkable change. Administration of thioperamide (30 microg ICV), an H3 antagonist, increased the threshold, although systemic administration of the agent (3.6 mg/kg IP) decreased it.


CONCLUSIONS
Blockade of supraspinal histamine H2 receptors or stimulation of spinal H3 receptors may contribute to alleviation of neuropathic pain.
Huang
Liang
L
Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Adachi
Naoto
N
Nagaro
Takumi
T
Liu
Keyue
K
Arai
Tatsuru
T
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004333:Drug Administration Routes; D006632:Histamine / Q000378:metabolism* / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D006636:Histamine Release; D008026:Ligation / Q000379:methods; D008297:Male; D009437:Neuralgia / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D011739:Pyrimethamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011968:Receptors, Histamine / Q000187:drug effects; D012584:Sciatic Nerve
D006633:Histamine Antagonists; D011968:Receptors, Histamine; C006308:metoprine; D006632:Histamine; D011899:Ranitidine; D011739:Pyrimethamine