Spinal 5-HT1A Receptor Plays A Major Role In Directing Serotonergic Modulation Toward Inhibition On Mechanical Allodynia Of Carrageenan Inflammation | 53865
Journal of Pain & Relief
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Introduction: Descending serotonergic projections may facilitate or inhibit nociceptive processing in the spinal cord depending
on several factors. Unlike other pain states, spinal 5-hydroxytryptamine 3 receptors (5-HT3R) were shown to play a limited role
in nociceptive transmission of carrageenan-induced inflammatory pain. Instead, a facilitatory role of 5-HT1AR and 5-HT1BR
in spinal nociceptive processing was observed during early-phase of carrageenan model. Although, the maximum release of
5-HT in spinal cord reaches the maximum 2-3 hours after carrageenan injection (early-phase), its release returns to baseline
Aim: To identify the role of Spinal 5-HT1A receptor in directing serotonergic modulation toward inhibition on mechanical
allodynia of carrageenan inflammation.
Methods: Effects of intrathecal (i.t.) nonspecific 5-HTR agonist, subtype agonist or antagonists (5-HT1AR, 5-HT1BR,
5-HT3R), and 5,7-dihydroxytryptamine (5,7-DHT, a serotonergic neurotoxin) on mechanical allodynia were tested for earlyand
Results: Lesioning spinal serotonergic projections with 5,7-DHT induced a significant increase in the intensity of mechanical
allodynia at both early and late-phase. This increase was attenuated by i.t. 5-HT. Also, i.t. 5-HT itself produced a significant
antiallodynic effect in late-phase, but not in early-phase. Similarly, i.t. 5-HT1AR agonist (8-OH-DPAT) attenuated the intensity
of late-phase allodynia in a dose-dependent manner which was antagonized by 5-HT1AR antagonist (WAY-100635), but
produced no effect on the early-phase allodynia. However, other agonists or antagonists of 5-HT1BR and 5-HT3R did not
produce any anti or pro-allodynic effects.
Conclusion: Descending serotonergic modulation plays a vital role in inhibition of nociceptive processing during late-phase
allodynia, which involves spinal 5-HT1A, but not 5-HT1B or 5-HT3 receptors in carrageenan-induced inflammation. However,
the defined role of 5-HT1A and serotonergic inhibition during early-phase remains undetermined.