Antinociceptive effects of central and systemic administrations of nicotine in the rat

Sahley, Tony L.; Berntson, Gary G.

doi:10.1007/bf00492216

Cited by 173 publications

(72 citation statements)

References 14 publications

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“…Hyperalgesia and͞or irritation have been observed after central injections of nicotinic agonists (8)(9)(10), systemic injections of subanalgesic doses (11), and intrathecal applications (12,13). This intrathecal effect is associated with significant increases in excitatory transmitter release (14), and both nicotinic and glutamate receptor antagonists can decrease this hyperalgesia (15,16).…”

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confidence: 99%

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Genzen

McGehee

2003

Proc. Natl. Acad. Sci. U.S.A.

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Spinal administration of nicotinic agonists can produce both hyperalgesic and analgesic effects in vivo. The cellular mechanisms underlying these behavioral phenomena are not understood. As a possible explanation for nicotinic hyperalgesia, we tested whether nicotinic acetylcholine receptors (nAChRs) could enhance excitatory transmission onto spinal cord dorsal horn neurons. Whole-cell patch-clamp recordings were performed in neonatal rat spinal cord slices. Activation of nAChRs enhanced glutamatergic synaptic transmission in 59% of dorsal horn neurons tested, and this effect was blocked by methyllycaconitine (10 nM), suggesting a key role for ␣7 nAChRs. Inhibition of acetylcholinesterase with methamidophos also enhanced transmission, demonstrating a similar effect of endogenous acetylcholine. nAChR activation also enhanced transmission by dorsal root entry zone stimulation, suggesting that ␣7 nAChRs on the central terminals of DRG afferents mediate this effect. Paired pre-and postsynaptic stimulation induced long-term potentiation of excitatory inputs to some of the dorsal horn neurons. Long-term potentiation induction was much more prevalent when nicotine was applied during stimulation. This effect also depended on both ␣7 nAChRs and N-methyl-D-aspartate glutamate receptors. Our findings demonstrate that ␣7 nAChRs can contribute to both short-and long-term enhancement of glutamatergic synaptic transmission in the spinal cord dorsal horn and provide a possible mechanism for nicotinic hyperalgesia.E ffective pain management is a major challenge for modern healthcare. Most pain medications fall under two classes of compounds, opioids and nonsteroidal antiinflammatory drugs. Recently, structural analogs of nicotine have also demonstrated strong analgesic potency (1, 2). Although these agents may provide alternate pain therapies, a number of issues remain to be resolved, such as addictive profiles and side effects, including paradoxical hyperalgesia. Considerable research has focused on the analgesic effects of nicotine and its analogs (2-7), yet the mechanisms underlying nicotinic hyperalgesia are not well understood.Hyperalgesia and͞or irritation have been observed after central injections of nicotinic agonists (8-10), systemic injections of subanalgesic doses (11), and intrathecal applications (12,13). This intrathecal effect is associated with significant increases in excitatory transmitter release (14), and both nicotinic and glutamate receptor antagonists can decrease this hyperalgesia (15, 16). Although dorsal horn neurons are excited by nicotine (17), it is not known which subtypes of nicotinic acetylcholine receptors (nAChRs) are expressed by dorsal horn neurons or on presynaptic afferent terminals. For example, nicotinic enhancement of synaptic activity has been noted in the spinal cord dorsal horn (SCDH) in mice that lack the ␣4 nAChR subunit, but the nAChR subtype(s) that mediate this effect is unknown (5).Neuronal nAChRs are pentameric ligand-gated ion channels, and molecular cloning has identified nin...

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mentioning

confidence: 99%

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Genzen

McGehee

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…nAChRs are extensively distributed in central nervous system (CNS) and peripheral sites. Although most reports focus on the central sites of the analgesic action of nicotinic agonists (Damaj et al 1998, Khan et al 1994, Sahley and Berntson 1979, α-7 nAChRs were found in peripheral sites, such as ganglion neurons of the dorsal root (Boyd et al 1991, Hu and Li 1997, Genzen et al 2001.…”

Section: Discussionmentioning

confidence: 99%

Antinociceptive and anti-inflammatory effects of a Geissospermum vellosii stem bark fraction

Lima

Costa

Silva

et al. 2016

An. Acad. Bras. Ciênc.

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Geissospermum vellosii (Pao pereira) is a Brazilian tree whose stem barks are rich in indole alkaloids that present intense anticholinesterase activity. The present study evaluated the effects of a stem bark fraction (PPAC fraction) and ethanolic extract (EE) of Pao pereira in classic murine models of infl ammation and pain. The EE and PPAC fraction, both at a dose of 30 mg/kg, signifi cantly reduced mice abdominal constriction induced by acetic acid by 34.8% and 47.5%, respectively. In the formalin test, EE (30 mg/ kg) and PPAC fraction (30 and 60 mg/kg) inhibited only the second phase, by 82.8%, 84.9% and 100%, respectively. Compared with indomethacin, similar doses of EE or PPAC fraction were approximately twice as effective in causing antinociception. PPAC fraction was not effective in the hot plate test but reduced the infl ammatory response at the second (50.6%) and third (57.8%) hours of rat paw edema induced by carrageenan. Antihyperalgesic activity was observed within 30 min with a peak at 2 h (60.1%). These results demonstrate that compounds in PPAC fraction have anti-infl ammatory and antinociceptive activity by a mechanism apparently unrelated to the opioid system. Regardless of similar responses to indomethacin, the effects of PPAC fraction are mainly attributed to acetylcholine actions.

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“…But inflammatory reactions in peripheral tissues and action change in dorsal root of spine are the main reasons of delayed phase. The main reason of pain in second phase is because of inflammatory reactions (Sahley and Berntson, 1979;Shibata et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…The results of this study have shown that MC extract can induce analgesia in mice. Also, it shows that MC has analgesic effects in both phases of formalin test that indicate that MC could have central nervous system (CNS) and local effects (Aceto et al, 1980;Murray and Brater, 1993;Phan et al, 1973;Sahley and Berntson, 1979). Studies on laboratory animals have shown that MC extract has antiinflammatory, antispasmodic and antidisquiet effects that are predicted in traditional medicine (Besson and Chaouch, 1987;Viola et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Antinociceptive effect of Matricaria chamomilla on vincristine-induced peripheral neuropathy in mice

Nouri¹

2012

Afr. J. Pharm. Pharmacol.

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Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus, effective therapeutic strategy is required. In this study, the antinociceptive effect of Matricaria chamomilla (MC) hydroalcoholic extract and morphine on vincristine-induced peripheral neuropathy model in mice has been investigated. Experiments were performed on 60 Naval Medical Research Institute (NMRI) male mice. Mouse subsequently received daily intraperitoneal and intravenal injections of vincristine sulfate, saline and MC hydroalcoholic extract over 12 days, immediately following behavioral testing. For assessment of pain, formalin test was preformed. The effects of MC, morphine and vehicle (saline) 30 min before formalin test on vincristine-induced neuropathy were evaluated. Administration of MC before formalin injection showed significant (P < 0.05) decrease of pain responses in both phases. Administration of vincristine produced significant (Pm < 0.05) increase in pain response in second phase of formalin test. Injection of MC and vincristine together has shown that MC is able to decrease the vincristine induced pain significantly (P < 0.05). Morphine decreased vincristine induced pain test significantly (P < 0.05). In comparison, morphine has analgesic effects in the first phase and MC has anti-inflammatory effects in the second phase of formalin test significantly (P < 0.05). These results suggest that MC may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

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Antinociceptive effects of central and systemic administrations of nicotine in the rat

Cited by 173 publications

References 14 publications

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Antinociceptive and anti-inflammatory effects of a Geissospermum vellosii stem bark fraction

Antinociceptive effect of Matricaria chamomilla on vincristine-induced peripheral neuropathy in mice

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