Vesna Pirec

Publications (4) View all

• Article: The combined effects of N-type calcium channel blockers and morphine on A delta versus C fiber mediated nociception.

  V Pirec, C E Laurito, Y Lu, D C Yeomans
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  ABSTRACT: Intrathecal mu opiates produce analgesia presynaptically by inhibiting calcium ion influx and postsynaptically by increasing potassium flux. Mu receptors are expressed on presynaptic terminals of unmyelinated (C), but not myelinated (A delta) nociceptors. Thus, mu-opioids such as morphine may act presynaptically to inhibit C, but not A delta, neurotransmission, and postsynaptically on dorsal horn cells that receive input from A delta and/or C fiber nociceptors. N-type calcium ion channel blockers, such as omega-conotoxin GVIA (omega-CTX), produce analgesia by impeding flux of calcium ions into A delta and C fiber nociceptor terminals. Thus, morphine and omega-CTX attenuated C fiber nociception additively, possibly indicating the same presynaptic site of action. Conversely, morphine and omega- CTX were supraadditively analgesic on an A delta test, indicating that these agents probably have different sites of action. We conclude that although intrathecal application of either morphine or omega-CTX attenuates both A delta and C fiber mediated nociception in rats, the combined effects are quite different for the two fiber types. Specifically, although coadministration of morphine with omega-CTX produces an additive, apparently presynaptic antinociception for C fiber-mediated responses, the combination produces a clearly supraadditive, and likely synergistic effect on A delta mediated nociception, probably by acting at pre and postsynaptic sites, respectively. Implications: This study demonstrates that combined spinal administration of mu opioids and N-type calcium channel blockers may be useful in providing analgesia for A delta mediated (first, sharp) pain while minimizing the side effects of both drugs.
  Anesthesia & Analgesia 02/2001; 92(1):239-43. · 3.29 Impact Factor
• Article: Differential antinociceptive effects of spinal opioids on foot withdrawal responses evoked by C fibre or A delta nociceptor activation.

  Y Lu, V Pirec, D C Yeomans
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  ABSTRACT: 1. Intrathecal application of mu, delta, and kappa opioids attenuate responses on several tests of animal nociception. However, the potency of these opioids differ depending on which tests were used. One factor contributing to these discrepancies is that different types of noxious stimuli activate different sets of nociceptor types, which may be differentially sensitive to opiate inhibition. To examine this hypothesis, we used a recently developed behavioural test which allows for differential assessment of nociception evoked by the activation of myelinated (A delta) and unmyelinated C thermonociceptors. 2. Administration of a kappa-selective agonist was ineffective on either type of response. Delta1 drugs were slightly more potent on C fibre-mediated responses than on A delta-mediated responses. 3. Intrathecal mu and delta2 drugs were antinociceptive on both A delta and C nociceptor-mediated responses. However, unlike the delta1 effects, the dose-response curves for mu and delta2 drugs were significantly more steep for A delta than for C fibre-mediated responses, potentially indicating differences in the mechanisms by which the drugs act on these 2 response types.
  British Journal of Pharmacology 08/1997; 121(6):1210-6. · 4.41 Impact Factor
• Article: Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: behavioral evidence.

  D C Yeomans, V Pirec, H K Proudfit
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  ABSTRACT: Several lines of evidence suggest that different classes of nociceptive afferents mediate the responses produced by different rates of noxious skin heating. More specifically, low skin heating rates evoke nociceptive responses that appear to be mediated by the activation of capsaicin-sensitive C-fiber nociceptors, whereas high skin heating rates appear to produce responses mediated by the activation of other nociceptors. This hypothesis was examined by both electrophysiological and behavioral experiments. This report describes the results of experiments designed to determine whether pharmacologic treatments that selectively alter the activity of C-fiber nociceptive afferents also produce selective effects on foot withdrawal responses to either high or low rates of noxious foot heating. The results of these experiments demonstrate that: (1) topical application of a low concentration of capsaicin, which sensitizes C-fiber nociceptors, selectively decreased the latency of responses to low heating rates; (2) topical application of a high concentration of capsaicin, that desensitizes C-fiber nociceptors, selectively increased the latency of responses to low heating rates; (3) low doses of systemic morphine, which selectively attenuate nociception produced by the activation of C-fiber nociceptors, selectively increased response latencies for low skin heating rates. These results support the conclusion that foot withdrawal responses evoked by low skin heating rates are mediated by the activation of capsaicin-sensitive C-fiber nociceptors and foot withdrawal responses evoked by high skin heating rates are mediated by the activation of other nociceptors. This conclusion is supported by the results of the accompanying electrophysiological study which provides direct evidence that low rates of skin heating preferentially activate C-fiber nociceptors while high rates of skin heating preferentially activate A delta nociceptors.
  Pain 12/1996; 68(1):133-40. · 5.78 Impact Factor
• Article: Effects of subanesthetic concentrations of nitrous oxide on cold-pressor pain in humans.

  V Pirec, T H Patterson, P Thapar, J L Apfelbaum, J P Zacny
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  ABSTRACT: Nitrous oxide (N2O) has analgesic properties as determined in both animal and human research. In the present study, we sought to determine whether N2O given in subanesthetic concentrations would reduce cold pressor (CP)-induced pain. A crossover, double-blind study was conducted in 10 healthy volunteers. Each subject participated in four separate sessions, and in each session the effects of one of four concentrations of N2O in oxygen (0, 20, 30, and 40%) were assessed. The duration of inhalation was 40 min, and within each session, subjects immersed their nondominant arm in water (2-3 degrees C) twice for 3 min (at 10 and 30 min intrainhalation). Pain intensity, the degree to which the pain was bothersome (measured on a verbal scale of 0-10, 0 = "not at all" and 10 = "extremely" painful/bothersome), and pain quality [measured by the short-form McGill Pain Questionnaire (SF-MPQ)] were assessed during the forearm immersion. Mood effects were measured with the use of visual analogue scales (VAS) in the presence and absence of pain. Self-reported pain intensity and bothersomeness, SF-MPQ ratings of "sharp pain" and "throbbing pain," and VAS rating of "unpleasant bodily sensations" were significantly reduced by N2O (p < 0.05) in a concentration-dependent manner. Nitrous oxide had a number of effects on mood (e.g., increased VAS ratings of "stimulated," "high," "coasting," "carefree," and "having pleasant bodily sensations"). The cold-water immersion also influenced mood, but had little impact on modulating N2O effects.(ABSTRACT TRUNCATED AT 250 WORDS)
  Pharmacology Biochemistry and Behavior 51(2-3):323-9. · 2.53 Impact Factor