Differential antinociceptive effects of spinal opioids on foot withdrawal responses evoked by C fibre or Aδ nociceptor activation

Abstract

1 Intrathecal application of m, d, and k opioids attenuate responses on several tests of animal nociception. However, the potency of these opioids di er depending on which tests were used. One factor contributing to these discrepancies is that di erent types of noxious stimuli activate di erent sets of nociceptor types, which may be di erentially sensitive to opiate inhibition. To examine this hypothesis, we used a recently developed behavioural test which allows for di erential assessment of nociception evoked by the activation of myelinated (Ad) and unmyelinated C thermonociceptors. 2 Administration of a k-selective agonist was ine ective on either type of response. d 1 drugs were slightly more potent on C ®bre-mediated responses than on Ad-mediated responses. 3 Intrathecal m and d 2 drugs were antinociceptive on both Ad and C nociceptor-mediated responses. However, unlike the d 1 e ects, the dose-response curves for m and d 2 drugs were signi®cantly more steep for Ad than for C ®bre-mediated responses, potentially indicating di erences in the mechanisms by which the drugs act on these 2 response types.

Diverse immunocytochemical expression of opioid receptors in electrophysiologically defined cells of rat dorsal root ganglia

“…MOR agonists are much more potent against C fiber than Ad fiber nociception, while DOR agonists are relatively weaker against either nociceptive family. KOR agonists appeared to be ineffective hypalgesics for cutaneous nociceptors (Cooper et al, 1986;Yeomans and Proudfit, 1996;Lu et al, 1997). The presence of MOR-IR in all subclassified, cutaneous, Ad nociceptors is consistent with the behavioral and physiological observations noted, but cannot account for the very great differences in potency that were reported.…”

“…Given the specific identification of nociceptors that express multiple receptor protein, the contribution of heteromeric receptors can be directly assessed. A number of other, anatomical, physiological and methodological difficulties must also be considered to fully understand the interaction of opiate analgesics with the pain system (see Lu et al, 1997).…”

Nociception and inflammatory hyperalgesia evaluated in rodents using infrared laser stimulation after Trpv1 gene knockout or resiniferatoxin lesion

“…However, additional factors, such as differences in fiber density and spatial summation, need to be considered before reaching this conclusion. C-fibers outnumber Aδ fibers in rat paw skin, and the area of the C-fiber stimulus used in this study was substantially larger (−10−) than that of the Aδ stimulus [23,26,29,40,43]. In addition, these data were recorded in awake, unrestrained rats with a noncontact thermal stimulus.…”

Spinal μ-Opioid Receptor-Expressing Dorsal Horn Neurons: Role in Nociception and Morphine Antinociception

“…Based on the well known expression of MOR on C fiber primary afferent terminals (Lamotte et al, 1976;Aicher et al, 2000) and the preferential antinociceptive effect of morphine on C fiber-mediated pain (Lu et al, 1997), we had anticipated that selective loss of MOR-expressing interneurons might not affect the antinociceptive effect of intrathecal morphine in the 44°C hotplate test, which elicits C nociceptor-mediated nocifensive reflex responses (Vierck et al, 2004). Because our anatomic observations (above) indicate that DRG neurons and their central terminals were unaffected by lumbar intrathecal Derm-sap and the behavioral data show decreased morphine antinociception in Derm-sap-treated rats, we interpret the present results as calling into question the hypothesis that morphine acts by inhibiting primary afferent terminals (Aimone and Yaksh, 1989;Ueda et al, 1995;Kondo et al, 2005).…”

“…Morphine antinociception is often evaluated using innate reflex responses to high-intensity phasic thermal stimulation (tail flick, paw withdrawal). These methods are problematic for investigation of morphine, because high-intensity thermal stimuli elicit responses that correlate with excitation of A-␦ nociceptors (Vierck et al, 2002) that are relatively resistant to attenuation by morphine (Lu et al, 1997). Phasic thermal pain in humans and thermal operant escape responses in animals to lower-intensity thermal stimuli produce sensations and nocifensive responses dominated by input from unmyelinated C nociceptors (Yeomans and Proudfit, 1996) that are highly sensitive to attenuation by systemic morphine (Cooper et al, 1986;.…”