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Blockade of neuronal nitric oxide synthase (nNOS) within the periaqueductal gray (PAG) differentially modulates neurotransmission and cardiovascular responses during mechanical and thermal nociception
Author(s) -
Karlsson Gudbjorn A,
Chaitoff Kevin A,
Hossain Shamma,
Bohlke Mark,
Maher Timothy John,
Ally Ahmmed
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a474-d
Subject(s) - nociception , chemistry , glutamate receptor , nitric oxide synthase , nitric oxide , periaqueductal gray , stimulation , microdialysis , neurotransmission , medicine , gabaergic , endocrinology , central nervous system , receptor , biochemistry , extracellular , midbrain
Nitric oxide (NO) is synthesized from L‐arginine using NO synthase (NOS) that exists as 3 isoforms: endothelial (eNOS), neuronal (nNOS), & inducible (iNOS). We examined the role of nNOS within the dorsolateral PAG on cardiovascular responses and glutamate and GABA concentrations during mechanical and thermal nociception in anesthetized rats. Mechanical stimulus was applied by a bilateral hindpaw pinch (5 sec) that increased mean arterial pressure (MAP), heart rate (HR), & glutamate within PAG by 24±4 mmHg, 41±7 bpm, & 10.7±1.3 ng/μl, respectively (n=10). GABA concentrations decreased by 1.9±0.5 ng/μl. Microdialysis of a selective nNOS antagonist, 1‐(2‐trifluoromethylphenyl)‐imidazole (TFMI; 10.0 μM), into the PAG had no effect on MAP, HR, glutamate & GABA values during a mechanical stimulation. Thermal stimulus was generated by immersing a hindpaw metatarsus in a water‐bath at 52°C (5 sec). Glutamate, MAP and HR increased by 14.4±2 ng/μl, 45±6 mmHg & 47±7 bpm while GABA decreased by 2.8±0.6 ng/μl (n=10). Administration of TMFI into dPAG augmented cardiovascular responses and glutamate increase and attenuated GABA changes during thermal nociception. Results demonstrate that nNOS within the PAG plays a differential role in modulating cardiovascular responses and glutamatergic/GABAergic neurotransmission during thermal and mechanical nociception.