Abstract
Cannabinoid CB1 receptors have been found in the superficial dorsal horn of the spinal cord, particularly the substantia gelatinosa (SG), which is thought to play a pivotal role in modulating nociceptive transmission. Although cannabinoids are known to inhibit excitatory transmission in SG neurons, their effects on inhibitory transmission have not yet been examined fully. In order to know further about a role of cannabinoids in regulating nociceptive transmission, we examined the effects of cannabinoids on inhibitory transmissions in adult rat SG neurons using whole-cell voltage-clamp recordings. Anandamide (10 μM) superfused for 2 min reduced glycinergic and GABAergic electrically-evoked inhibitory postsynaptic current (IPSC) amplitudes; these actions persisted for more than 6 min after washout. Similar actions were produced by cannabinoid-receptor agonist WIN55,212-2 (5 μM) and 2-arachidonoyl glycerol (20 μM). The evoked IPSC amplitudes reduced by anandamide recovered to the control level following superfusion of CB1-receptor antagonist SR141716A (5 μM). A ratio of the second to first evoked IPSC amplitude in paired-pulse experiments was increased by anandamide (10 μM). The frequencies of glycinergic and GABAergic spontaneous IPSCs were reduced by anandamide (10 μM) without a change in their amplitudes. It is concluded that cannabinoids depress inhibitory transmissions in adult rat SG neurons by activating CB1 receptors in nerve terminals. This action could contribute to the modulation of nociceptive transmission by cannabinoids.
Highlights
Cannabinoids play an important role in a variety of physiological phenomena including antinociception
On the other hand, when the VH was shifted to 0 mV, Spontaneous IPSCs (sIPSCs) could be encountered in all neurons tested, where no spontaneous excitatory postsynaptic currents (EPSCs) were invisible owing to the reversal potential for EPSCs to be close to 0 mV [38]
Neither the frequency nor the amplitude of sIPSCs was significantly affected following the application of TTX (0.5 μM; data not shown), indicating that the production of the sIPSCs was independent of the spontaneous activities of neurons presynaptic to substantia gelatinosa (SG) neurons
Summary
Cannabinoids play an important role in a variety of physiological phenomena including antinociception (for review see [1]-[4]). Cannabinoids produce antinociception in acute pain models through the activation of the cannabinoid receptors [1] [3] [4]. Applying the prototypical cannabinoid Δ9-tetrahydrocannabinol resulted in antinociception in the tail-flick test in adult rats [5]. A mixed CB1/CB2 receptor agonist WIN55,212-2 (WIN-2) produced a similar antinociceptive effect [6]. Such behavioral results are possibly due to the activation of the CB1 receptor in the spinal dorsal horn, because expression of this receptor has been demonstrated there by in situ hybridization [7], agonist binding [8] and immunohistochemistry [9]-[12]. A selective CB1-receptor antagonist SR141716A enhanced nociceptive responses of rat spinal dorsal horn neurons [13]
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