Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 43 (6), 834-45

Involvement of Spinal α2 -Adrenoceptors in Prolonged Modulation of Hind Limb Withdrawal Reflexes Following Acute Noxious Stimulation in the Anaesthetized Rabbit

Affiliations

Involvement of Spinal α2 -Adrenoceptors in Prolonged Modulation of Hind Limb Withdrawal Reflexes Following Acute Noxious Stimulation in the Anaesthetized Rabbit

John Harris. Eur J Neurosci.

Abstract

The role of spinal α2 -adrenoceptors in mediating long-lasting modulation of hind limb withdrawal reflexes following acute noxious chemical stimulation of distant heterotopic and local homotopic locations has been investigated in pentobarbitone-anaesthetized rabbits. Reflexes evoked in the ankle extensor muscle medial gastrocnemius (MG) by electrical stimulation of the ipsilateral heel, and reflexes elicited in the ankle flexor tibialis anterior and the knee flexor semitendinosus by stimulation at the base of the ipsilateral toes, could be inhibited for over 1 h after mustard oil (20%) was applied to either the snout or into the contralateral MG. The heel-MG response was also inhibited after applying mustard oil across the plantar metatarsophalangeal joints of the ipsilateral foot, whereas this homotopic stimulus facilitated both flexor responses. Mustard oil also caused a significant pressor effect when applied to any of the three test sites. The selective α2 -adrenoceptor antagonist, RX 821002 (100-300 μg, intrathecally), had no effect on reflexes per se, but did cause a decrease in mean arterial blood pressure. In the presence of the α2 -blocker, inhibitory and facilitatory effects of mustard oil on reflexes were completely abolished. These data imply that long-lasting inhibition of spinal reflexes following acute noxious stimulation of distant locations involves activation of supraspinal noradrenergic pathways, the effects of which are dependent on an intact α2 -adrenoceptor system at the spinal level. These pathways and receptors also appear to be involved in facilitation (sensitization) as well as inhibition of reflexes following a noxious stimulus applied to the same limb.

Keywords: DNIC; RX 821002; descending inhibition; mustard oil; spinal cord.

Figures

Figure 1
Figure 1
Example electromyogram recordings and analysis time windows of reflex responses in (A) medial gastrocnemius (MG) and (B) semitendinosus (ST)/tibialis anterior (TA) to electrical stimulation of the heel and toes, respectively. Each record is the average of eight sweeps and the stimulus was applied at the beginning of each sweep. Placement of cursors for measurement of the voltage/time integral (area) of the response is indicated by the dashed lines.
Figure 2
Figure 2
Effect of the selective α2‐adrenoceptor antagonist RX 821002 on reflex responses (top panel) and cardiovascular parameters (bottom panel) (n = 10). For reflexes, column height represents the median response and error bars are 1st quartile values. For cardiovascular data, points are means and error bars are SEM. RX 821002 was given intrathecally (200–300 μg) at time 0.
Figure 3
Figure 3
Effect of repeated mustard oil application to the contralateral medial gastrocnemius (MG) muscle (• first injection; ∘ second injection) on heel–MG, toes–tibialis anterior (TA) and toes–semitendinosus (ST) reflexes in the absence (top panels) or presence (bottom panels) of RX 821002 (100–300 μg, intrathecally) prior to the second injection. Each point on the graphs represents the median of nine (no drug group) or 10 (RX 821002 group) experiments, and the vertical lines are either 1st or 3rd quartiles. Mustard oil was applied at 0 min. *Indicates a significant difference in the effect of mustard oil at equivalent time points before and after intrathecal RX 821002 (Wilcoxon tests, < 0.05).
Figure 4
Figure 4
Effect of repeated mustard oil application to the snout (• first application; ∘ second application) on heel–medial gastrocnemius (MG), toes–tibialis anterior (TA) and toes–semitendinosus (ST) reflexes in the absence (top panels) or presence (bottom panels) of RX 821002 (100–300 μg, intrathecally) prior to the second injection. Each point on the graphs represents the median of nine (no drug group) or 10 (RX 821002 group) experiments, and the vertical lines are either 1st or 3rd quartiles. Mustard oil was applied at 0 min. *Indicates a significant difference in the effect of mustard oil at equivalent time points before and after intrathecal RX 821002 (Wilcoxon tests, < 0.05).
Figure 5
Figure 5
Effect of repeated mustard oil application to the plantar metatarsophalangeal (MT) joints (• first application; ∘ second application) on heel–medial gastrocnemius (MG), toes–tibialis anterior (TA) and toes–semitendinosus (ST) reflexes in the absence (top panels) or presence (bottom panels) of RX 821002 (100–300 μg, intrathecally) prior to the second injection. Each point on the graphs represents the median of nine (no drug group) or 10 (RX 821002 group) experiments, and the vertical lines are either 1st or 3rd quartiles. Mustard oil was applied at 0 min. *Indicates a significant difference in the effect of mustard oil at equivalent time points before and after intrathecal RX 821002 (Wilcoxon tests, < 0.05).
Figure 6
Figure 6
Effect of mustard oil applied to the metatarsophalangeal (MT) joints on mean arterial blood pressure (top panel) and heart rate (bottom panel) before (•) and after (∘) administration of RX 821002 (100–300 μg, intrathecally). Each point on the graph represents the mean of 10 experiments, and error bars are SEM. Mustard oil was applied at 0 min, and RX 821002 was administered 20–30 min before the second mustard oil stimulus was applied. Mustard oil caused a significant increase in blood pressure and heart rate before but not after administration of RX 821002.

Similar articles

See all similar articles

Cited by 1 article

References

    1. Alarcón G. & Cervero F. (1989) Effects of two anaesthetic regimes on the heterotopic inhibition of rat dorsal horn neurones. J. Physiol., 416, 19P. - PubMed
    1. Andersen O.K., Sonnenborg F.A. & Arendt‐Nielsen T. (1999) Modular organization of human leg withdrawal reflexes elicited by electrical stimulation of the foot sole. Muscle Nerve, 22, 1520–1530. - PubMed
    1. Baba Y., Kohase H., Oono Y., Fujii‐Abe K. & Arendt‐Nielsen L. (2012) Effects of dexmedetomidine on conditioned pain modulation in humans. Eur. J. Pain, 16, 1137‐1147. - PubMed
    1. Blessing W.W. (1997) The Lower Brainstem and Bodily Homeostasis. Oxford University Press, Oxford.
    1. Blessing W.W., Chalmers J.P. & Howe P.R.C. (1978) Distribution of catecholemine‐containing cell bodies in the rabbit central nervous system. J. Comp. Neurol., 179, 407–424. - PubMed

Substances

Feedback