The somatostatin analogue octreotide inhibits capsaicin-mediated activation of nociceptive primary afferent fibres in spinal cord lamina II (substantia gelatinosa).
Somatostatin (SST) in spinal cord has been linked with the inhibition of nociceptive neurotransmission in several experimental paradigms. The SST2 receptor (SSTR2) is the main SST receptor subtype in the superficial dorsal horn (DH) and is activated, besides to the naïve peptide, by the SST synthetic analogue octreotide (OCT). In the present work, we have studied the central effects of SSTR2 activation on capsaicin (CAP)-induced glutamate release in mouse DH. In neurons of the lamina II of DH, CAP (2 μM) induced a strong increase of mEPSC frequency that was significantly reduced (70%) by OCT. SSTR2 involvement was assessed by using the specific antagonist CYN 154806. No differences were observed between frequency increase in CAP alone vs. CAP in the presence of CYN 154806+OCT. The effect of OCT was further investigated by studying c-fos expression in spinal cord slices. The CAP-induced increase in density of Fos immunoreactive nuclei in the superficial DH was strongly prevented by OCT. SSTR2a (a splicing variant of SSTR2) immunoreactivity was found in both pre- and post-synaptic compartments of laminae I-II synapses. By light and electron microscopy, SSTR2a was mainly localized onto non-peptidergic isolectin B4 (IB4)-positive primary afferent fibres (PAFs). A subset of them was also found to express the CAP receptor TRPV1. These data show that the SST analogue OCT inhibits CAP-mediated activation of non-peptidergic nociceptive PAFs in lamina II. Our data indicate that SSTR2a plays an important role in the pre-synaptic modulation of central excitatory nociceptive transmission in mouse.
Department of Veterinary Morphophysiology, Via Leonardo da Vinci 44, 10095 Grugliasco, Italy.
Ileana
I
Bencivinni
Francesco
F
Ferrini
Chiara
C
Salio
Massimiliano
M
Beltramo
Adalberto
A
Merighi
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D051379:Mice; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D018689:Sensory System Agents / Q000494:pharmacology*; D013376:Substantia Gelatinosa / Q000187:drug effects* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects
D017481:Receptors, Somatostatin; D018689:Sensory System Agents; C093733:somatostatin receptor 2; D015282:Octreotide; D002211:Capsaicin