Vagal modulation of spinal nicotine-induced inhibition of the inflammatory response mediated by descending antinociceptive controls
Introduction
Pain, such as that associated with inflammation, can produce inhibition of an inflammatory response, an effect mediated by neuroendocrine mechanisms (Green et al., 1997, Miao et al., 2000, Miao and Levine, 1999). This feedback inhibition of inflammation is under potent control by afferent activity in the subdiaphragmatic vagus nerve (Miao et al., 1997b). Thus, subdiaphragmatic vagotomy, or celiac plus celiac accessory branch vagotomy, produces a marked left shift in the dose-response curve for noxious stimulus-induced inhibition of plasma extravasation produced by bradykinin (Miao et al., 1997b), a potent inflammatory mediator (Bock and Longmore, 2000, Calixto et al., 2000). Vagotomy also enhances the potency of spinal intrathecal nicotine, which also inhibits bradykinin-induced plasma extravasation—possibly by acting on the central terminals of primary afferent nociceptors (Genzen et al., 2001, Miao et al., 2001, Steen and Reeh, 1993)—by six orders of magnitude (Miao et al., 1994). In this study we evaluate the hypotheses that: 1) descending antinociceptive controls inhibit intrathecal nicotine-induced attenuation of bradykinin-induced plasma extravasation, and 2) subdiaphragmatic vagotomy enhances noxious stimulus-induced inhibition of inflammation by decreasing activity in descending antinociceptive controls.
Section snippets
Methods
The experiments were performed on male Sprague-Dawley rats (300–400 g). Rats were anesthetized by intraperitoneal injection of sodium pentobarbital (65 mg/kg, Abbott Lab., Chicago, IL) for both surgical procedures and knee joint perfusion experiments. Animal care and use conformed to the NIH guidelines for the care and use of experimental animals. The University of California at San Francisco, Committee on Animal Research, approved all experimental protocols used in these experiments.
Intrathecal co-administration of α-adrenergic and opioid receptor antagonists potentiate the anti-inflammatory effect of intrathecal nicotine
To inhibit descending antinociceptive controls we intrathecally co-administered phentolamine (100 nmole in 10 μl) and naloxone (100 nmole in 10 μl), receptor antagonists for α-adrenergic and opioid receptors, respectively, known to be involved in descending antinociceptive controls. This produced a marked left shift in the dose response relationship for intrathecal nicotine-induced inhibition of bradykinin-induced plasma extravasation in the knee joint of the rat (Fig. 1(A); Statistics; Table 1
Discussion
We have previously demonstrated that activity in subdiaphragmatic vagal afferents potently attenuates noxious stimulus- and intrathecal nicotine-induced inhibition of inflammation (Miao et al., 1997b). However, the central nervous system circuitry by which vagal afferent activity modulates noxious stimulus-induced inhibition of the inflammatory response is still poorly understood. To evaluate underlying central nervous system circuitry, we have evaluated two hypotheses, that descending
Acknowledgements
This work was supported by a grant from the National Institutes of Health (AR32634).
References (40)
- et al.
Bradykinin antagonists: new opportunities
Current Opinion in Chemical Biology
(2000) - et al.
Kinins in pain and inflammation
Pain
(2000) - et al.
Experimentally induced muscle pain induces hypoalgesia in heterotopic deep tissues, but not in homotopic deep tissues
Brain Research
(1998) - et al.
Difference between the effect of acute and chronic surgical vagotomy on the cytoprotective action of atropine against indomethacin-induced mucosal lesions on the gastrointestinal tract in rats
Journal of Physiology, Paris
(1999) - et al.
Vagal afferent-mediated inhibition of a nociceptive reflex by intravenous serotonin in the rat
I Characterization Brain Research
(1990) Descending control of pain
Progress in Neurobiology
(2002)- et al.
Vagal afferent modulation of nociception
Brain Research Reviews
(1992) - et al.
Vagal afferent modulation of a nociceptive reflex in rats: involvement of spinal opioid and monoamine receptors
Brain Research
(1988) - et al.
Effects of electrical stimulation of vagal afferents on spinothalamic tract cells in the rat
Pain
(1991) - et al.
Effect of flurbiprofen on tissue levels of immunoreactive bradykinin and acute postoperative pain
Journal of Oral and Maxillofacial Surgery
(1993)
Dose-dependent antagonism of spinal opioid receptor agonists by naloxone and naltrindole: additional evidence for delta-opioid receptor subtypes in the rat
European Journal of Pharmacology
Footshock-induced analgesia: its opioid nature depends on the strain of rat
Brain Research
Chronic catheterization of the spinal subarachnoid space
Physiology and Behavior
Effect of vagotomy on expression of neuropeptides and histamine in rat oxyntic mucosa
Digestive Diseases and Sciences
The evaluation of increased vascular permeability in the skin of guinea pigs
Australian Journal of Experimental Biology and Medical Science
The dorsal horn: state-dependent sensory processing, plasticity and the generation of pain
Log-normal distribution of equiefective doses of norepinephrine and acetylcholine in several tissues
Journal of Pharmacology and Experimental Therapeutics
Inflammation: basic principles and clinical correlates
Dorsal root ganglion neurons express multiple nicotinic acetylcholine receptor subtypes
Journal of Neurophysiology
Negative feedback neuroendocrine control of inflammatory response in the rat is dependent on the sympathetic postganglionic neuron
Journal of Neuroscience
Cited by (6)
Involvement of acetylcholine receptors in cholinergic pathway-mediated protection against autoimmune diabetes
2019, Frontiers in ImmunologyAn α7 nicotinic acetylcholine receptor-selective agonist reduces weight gain and metabolic changes in a mouse model of diabetes
2010, Journal of Pharmacology and Experimental TherapeuticsNicotinic receptors as targets for therapeutic discovery
2007, Expert Opinion on Drug DiscoveryThoracic vagal ganglion and referred craniofacial pain: A case report and review
2007, International Journal of MorphologyPerioperative abstinence from cigarettes: Physiologic and clinical consequences
2006, AnesthesiologyMechanosensitive duodenal afferents contribute to vagal modulation of inflammation in the rat
2004, Journal of Physiology