The efficacy and potency of various classes of analgesic drugs is often dependent on the experimental model of pain used. For example, drugs that' act at serotonin(1a) receptors produce a strong antinociceptive effect on the hot-plate test, but are ineffective or produce hyperalgesic effects on the tail flick test. Similar differences have been observed for the antinociception produced by stimulation of various brain sites. One explanation for these different effects is that the drugs or the neurotransmitters released by brain stimulation produce selective effects on the nociception mediated by different types of nociceptors. Such a differential effect has been demonstrated for morphine, which selectively inhibits nociceptive responses produced by the activation of unmyelinated polymodal nociceptors. We have developed a rodent behavioral model which appears to selectively assess responses mediated by the activation of either C-polymodal or myelinated A-fiber nociceptors. Preliminary experiments have shown a preferential antinociceptive effect of serotonin(1a) agonists and morphine on responses produced by the activation of C-polymodal nociceptors and a preferential effect of alpha2- adrenoceptor agonists on responses produced by activation of myelinated nociceptors. We propose to perform behavioral and electrophysiological experiments to further establish the selectivity of this model. The model will then be used to examine the effects of opiate, sertonergic, and alpha-adrenergic agonists, and brainstem- stimulation, on nociceptive responses evoked by the activation of either C-polymodal or A nociceptors. To investigate whether the selectivity of these agents is mediated by inhibition of nociceptor afferent fibers, we will determine whether these treatments reduce the release of putative primary afferent neurotransmitters. These studies could provide important insights into the basic mechanisms underlying the antinociception produce by a variety of analgesic drugs. In addition, these studies may lead to the discovery of clinically useful drugs with selective analgesic effects on pain mediated by different nociceptors.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Illinois at Chicago
Schools of Medicine
United States
Zip Code
Cuéllar, Jason M; Borges, Paula M; Cuéllar, Vanessa Gabrovsky et al. (2013) Cytokine expression in the epidural space: a model of noncompressive disc herniation-induced inflammation. Spine (Phila Pa 1976) 38:17-23
Yeomans, David C; Lu, Ying; Laurito, Charles E et al. (2006) Recombinant herpes vector-mediated analgesia in a primate model of hyperalgesia. Mol Ther 13:589-97
Jones, Toni L; Sweitzer, Sarah M; Peters, Michael C et al. (2005) GABAB receptors on central terminals of C-afferents mediate intersegmental Adelta-afferent evoked hypoalgesia. Eur J Pain 9:233-42
Lu, Ying; Sweitzer, Sarah M; Laurito, Charles E et al. (2004) Differential opioid inhibition of C- and A delta- fiber mediated thermonociception after stimulation of the nucleus raphe magnus. Anesth Analg 98:414-9, table of contents
Tzabazis, A; Kim, P H; Sweitzer, S M et al. (2004) Ameroid rings for gradual chronic constriction of the sciatic nerve in rats: contribution of different nerves to neuropathic pain. Brain Res Bull 64:127-32
Sweitzer, S M; Peters, M C; Ma, J Y et al. (2004) Peripheral and central p38 MAPK mediates capsaicin-induced hyperalgesia. Pain 111:278-85
Yeomans, David C; Jones, Toni; Laurito, Charles E et al. (2004) Reversal of ongoing thermal hyperalgesia in mice by a recombinant herpesvirus that encodes human preproenkephalin. Mol Ther 9:24-9
Sweitzer, Sarah M; Wong, Shirley M E; Peters, Michael C et al. (2004) Protein kinase C epsilon and gamma: involvement in formalin-induced nociception in neonatal rats. J Pharmacol Exp Ther 309:616-25
Sweitzer, Sarah M; Medicherla, Satyanarayana; Almirez, Ramona et al. (2004) Antinociceptive action of a p38alpha MAPK inhibitor, SD-282, in a diabetic neuropathy model. Pain 109:409-19
Jones, Toni L; Sweitzer, Sarah M; Wilson, Steven P et al. (2003) Afferent fiber-selective shift in opiate potency following targeted opioid receptor knockdown. Pain 106:365-71

Showing the most recent 10 out of 22 publications