Octreotide inhibits capsaicin-induced activation of C and Aδ afferent fibres in rat hairy skin in vivo

Abstract

1. The present study investigated whether the somatostatin receptor (SSTR) agonist, octreotide, could inhibit the activation of dorsal skin afferent fibres induced by local injection of capsaicin in the rat. 2. Single unit activity from Aδ mechano-heat sensitive (AMH; n = 41) and C mechano-heat sensitive (CMH; n = 30) afferents was recorded after their isolation in thin filaments from the dorsal cutaneous nerve branches. The effect of subcutaneous octreotide injection on the change in discharge rate and mechanical threshold induced by capsaicin was determined. 3. Capsaicin (0.05%) injection into the edge of the receptive field of both AMH and CMH units increased their discharge rate and decreased their mechanical threshold. Pre-injection of octreotide inhibited these responses, and co-application of SSTR antagonist, cyclosomatostatin, reversed the inhibitory effect of octreotide. 4. The present study provides electrophysiological evidence that the signal evoked by the somatostatin receptor inhibits the activation and mechanical sensitization evoked by capsaicin in the terminals in small-diameter sensory neurons.

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

“…Thus, J-2156 does not affect neuronal transmission under normal physiological conditions (Gorham et al, 2014b ; Schuelert et al, 2015 ). While the endogenous ligand, somatostatin is well-known for its inhibitory actions on primary afferent nerve fibers (Carlton et al, 2004 ; Guo et al, 2008 ; Wang et al, 2009 ; Luo et al, 2010 ; Wang J. et al, 2011 ), the peptidomimetic compound- J-2156 (Sándor et al, 2006 ) inhibits transient receptor potential vanilloid 1 (TRPV1) currents, activates G-protein coupled inwardly rectifying potassium channels (GIRK) and inhibits voltage stimulated calcium channels in rat DRG neurons by specifically acting on SST4 receptors (Gorham et al, 2014a , b ). It remains to be investigated whether J-2156 can inhibit the primary afferent nerve firing in the pathophysiological state of BCIBP.…”

Regulation of alternative VEGF-A mRNA splicing is a therapeutic target for analgesia

“…It is therefore somewhat surprising that VEGF-A 165 a altered mechanical but not thermal thresholds in the normal animal, given that TRPV1 is well-known as a thermal transducer molecule ( Caterina et al, 1997 ). Local capsaicin can however cause peripheral mechanical sensitization of cutaneous ( Li et al, 2008; Ren et al, 2005; Ren et al, 2006; Wang et al, 2011 ), deep tissue and visceral afferents ( Kiyatkin et al, 2013; Lam et al, 2009 ). The mechanism(s) through which TRPV1-dependent peripheral mechanical sensitization of afferents occurs are not known, but may be a consequence of altered nociceptor excitability, rather than directly affecting mechanotransduction per se ( Malykhina et al, 2012; Raouf et al, 2012 ).…”

Somatostatin and its 2A Receptor in Dorsal Root Ganglia and Dorsal Horn of Mouse and Human: Expression, Trafficking and Possible Role in Pain

“…This is a peripheral action on DRG neurons, since Oct does not penetrate the blood–brain-barrier [20,48]. Moreover, Oct attenuates swelling and mechanical hyperalgesia in a mouse model of immune-mediated arthritis, an effect not seen in sst2A-KO mice [24], as well as capsaicin-induced nociceptor activity and nociceptive behavior in vitro and in vivo [94,95]. …”