Differential effects of the cannabinoid receptor agonist, WIN 55,212-2, on lamina I and lamina V spinal trigeminal nucleus caudalis neurons

Abstract

Direct application of cannabinoids to the medullary dorsal horn (MDH) inhibits lamina V nociceptive neurons. The present study compared the effect of the cannabinoid receptor agonist, WIN 55,212-2 (WIN-2) on the activity of lamina I and lamina V MDH neurons using extracellular single unit recording in anesthetized rats. Activity evoked by a contact thermode was measured before and after local application of WIN-2 (0.5-2.0 μg/μl) to the brainstem. Fast and slow heat ramps were used to differentiate between activity evoked primarily by A-delta and C primary afferent fibers, respectively. In lamina V neurons, WIN-2 produced a concentration dependent decrease in activity evoked by both fast and slow heat, reaching significance at 1.0 μg/μl. In lamina I neurons, WIN-2 administration inhibited slow heat evoked activity beginning at 1.0 μg/μl but had no significant effect on fast heat evoked activity, even at the highest concentration (2.0 μg/μl). In separate experiments, the effect of intrathecal administration of WIN-2 to the MDH on head withdrawal latencies elicited by fast and slow heat ramps applied to the whisker pad was assessed in lightly anesthetized rats. Head withdrawal latencies elicited by slow but not fast heat stimulation were increased by WIN-2. Taken together, these results emphasize the importance of lamina I neurons in the control of a nociceptive heat-evoked reflex.

Attenuation of cannabinoid-induced inhibition of medullary dorsal horn neurons by a kappa-opioid receptor antagonist

“…Behavioral withdrawal latencies were measured following fast and slow heat ramps applied to the whisker pad region. In agreement with our previous results (Ogawa and Meng, 2009), intrathecal administration of WIN-2 to the C1 region increased head withdrawal latencies only to the slow heat ramp (Fig 4A & B). The antinociception produced by WIN-2 was prevented by prior administration of either the CB1 antagonist SR141716 or the kappa opioid receptor antagonist nor-BNI (Fig 4A).…”

“…In a previous study, we demonstrated WIN-2 differentially inhibits MDH neurons based on their laminar location (Ogawa and Meng, 2009). In lamina I neurons, WIN-2 inhibited activity evoked by slow but not fast heat ramps.…”

“…Several studies have shown inhibition of spinal and medullary dorsal horn (MDH) neurons following administration of cannabinoid receptor agonists (Akerman et al, 2007; Drew et al, 2000; Hohmann et al, 1995; Hohmann et al, 1998; Hohmann et al, 1999; Johanek and Simone, 2005; Kelly and Chapman, 2003; Ogawa and Meng, 2009; Papanastassiou et al, 2004). It remains unknown, however, whether this inhibition involves the endogenous release of a KOR agonist.…”

“…It remains unknown, however, whether this inhibition involves the endogenous release of a KOR agonist. Recently, we have demonstrated inhibition of noxious thermal stimulation evoked activity of MDH neurons located in both superficial and deep laminae following local brainstem application of the CB1/CB2 receptor agonist WIN 55,212-2 (WIN-2) (Ogawa and Meng, 2009). Identical thermal stimuli were also used to demonstrate the ability of WIN-2 to inhibit the head withdrawal reflex.…”

Astroglia in Medullary Dorsal Horn (Trigeminal Spinal Subnucleus Caudalis) Are Involved in Trigeminal Neuropathic Pain Mechanisms

“…Our previous procedures (Ogawa and Meng, 2009) were used to study heat hyperalgesia and the effect of FA. Briefly, a soft microsilicon tube was inserted intrathecally from the L5 into the C1 level at 4 d before behavioral testing in IANX or sham-control rats; the IAN transection or sham operation had been performed 3 d before microsilicon tube insertion.…”