Background and Aims: Chronic low back pain (LBP) ranks among the most common reasons for patient visits to healthcare providers. The somatostatin receptor type 4 (SST4) agonist, J-2156 [(1’S,2S)-4amino-N-(1’-carbamoyl-2’-phenylethyl)-2-(4”-methyl-1”-naphthalenesulfonylamino)butanamide], is an agonist with nanomolar binding affinity at the human SST4 receptor and that has approximately 300-fold selectivity over other somatostatin receptors. Hence, our aim was to assess the efficacy of J-2156 for the relief of chronic mechanical LBP in a rat model.

Methods: Animal ethics approval was from The University of Queensland. Groups of adult male Sprague-Dawley rats were anaesthetised and their lumbar L4/L5 and L5/L6 intervertebral discs (IVDs) were punctured (0.5 mm outer diameter, 2 mm-deep) 10 times per disc. Sham-rats underwent similar surgery without disc puncture. On day 28 post model induction, rats received single bolus doses of J-2156 or vehicle in a blinded manner according to a wash-out protocol that had a 2-day washout period between three successive doses of either J-2156 or vehicle. Anti-hyperalgesia was assessed at L4/L5 (primary hyperalgesia) and at L1 (secondary hyperalgesia) for 3 h post-dose administration and the tester was blinded to administered treatment.

Results: For LBP-rats, there was temporal development of mechanical hyperalgesia in the lumbar axial deep tissues at L4/L5 and L1 that was fully developed by day 21 and that persisted until at least day 49 post-surgery. J-2156 alleviated both primary and secondary hyperalgesia in LBP-rats whereas vehicle was inactive.

Conclusions: The SST4 receptor is promising as a target for discovery of novel analgesics for alleviation of chronic LBP.

THE SELECTIVE SOMATOSTATIN TYPE 4 (SST<sub>4</sub>) RECEPTOR AGONIST, J-2156, ALLEVIATES PRIMARY AND SECONDARY MECHANICAL HYPERALGESIA IN A RAT MODEL OF CHRONIC MECHANICAL LOW BACK PAIN

THE SELECTIVE SOMATOSTATIN TYPE 4 (SST4) RECEPTOR AGONIST, J-2156, ALLEVIATES PRIMARY AND SECONDARY MECHANICAL HYPERALGESIA IN A RAT MODEL OF CHRONIC MECHANICAL LOW BACK PAIN

THE SELECTIVE SOMATOSTATIN TYPE 4 (SST₄) RECEPTOR AGONIST, J-2156, ALLEVIATES PRIMARY AND SECONDARY MECHANICAL HYPERALGESIA IN A RAT MODEL OF CHRONIC MECHANICAL LOW BACK PAIN