The three isoforms of nitric oxide synthase distinctively affect mouse nocifensive behavior.
Nitric oxide synthases (NOSs) have been shown to modulate thermal hyperalgesia and mechanical hypersensitivity in inflammatory and neuropathic pain. However, little is known about the effect of NOSs on baseline function of sensory nerve fibers. Using genetic deficiency and pharmacologic inhibition of NOSs, we examined the impact of the three isoforms NOS1, NOS2, and NOS3 on baseline nocifensive behavior by measuring current vocalization threshold in response to electrical stimulation at 5, 250, 2000 Hz that preferentially stimulate C, Aδ, and Aβ fibers. In response to 5, 250 and 2000 Hz, NOS1-deficient animals had significantly higher current vocalization thresholds compared with wild-type. Genetic deficiency of NOS2 was associated with higher current vocalization thresholds in response to 5 Hz (C-fiber) stimulation. In contrast, NOS3-deficient animals had an overall weak trend toward lower current vocalization thresholds at 5 Hz and significantly lower current vocalization threshold compared with wild-type animals at 250 and 2000 Hz. Therefore, NOSs distinctively affect baseline mouse current vocalization threshold and appear to play a role on nocifensive response to electrical stimulation of sensory nerve fibers.
Division of Anesthesiology and Pain Medicine, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, Washington, DC 20010, United States.
Julia
J
Finkel
Virginia
V
Guptill
Alfia
A
Khaibullina
Nicholas
N
Spornick
Olavo
O
Vasconcelos
David J
DJ
Liewehr
Seth M
SM
Steinberg
Zenaide M N
ZM
Quezado
D000704:Analysis of Variance; D000818:Animals; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007527:Isoenzymes; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis; D059225:Nociception / Q000502:physiology*; D010147:Pain Measurement; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism; D014828:Vocalization, Animal / Q000502:physiology*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester