Spinal Subarachnoid Injection of Somatostatin Causes Neurological Deficits and Neuronal Injury in Rats
Abstract
Intrathecal administration of somatostatin has recently been clinically investigated as a means to treat intractable pain in humans. Significant reductions in patient pain scores were recorded following bolus i.t. injections of 152.6 nmol of somatostatin, followed by i.t. infusions of 6.1-30.5 nmol/h. The present findings signal a need for caution and more comparative data before somatostatin is further used as a spinal analgesic in humans. The tetradecapeptide somatostatin produced dose-related neurological deficits following subarachnoid injection in the lumbar spinal cords of rats. Lower pharmacological doses (1.6 and 3.1 nanomole (nmol) i.t.) of somatostatin caused only transient deficits, while higher doses (6.2-25 nmol, i.t.) caused persistent deficits characterized by motor and sensory impairments in hindlimbs and tail, hindlimb edema, priapism, bladder atony with infarction, and urinary incontinence. Pretreatment with 0.3 nmol of the somatostatin receptor antagonist cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Brl)) blocked the hindlimb paralytic effects of 3.1 and 6.2 nmol of somatostatin, and significantly improved neurological recovery injection of12.5 nmol of somatostatin. Higher doses of the antagonist produced hindlimb paralysis by itself. Neuroanatomical evaluations revealed extensive cell loss and necrosis in the lumbosacral spinal cords of rats paralyzed by 25 nmol of somatostatin. Collectively, these results suggest that through interactions with a receptor, somatostatin destroys neurons involved in diverse spinal cord functions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1988
- Accession Number
- ADA195986
Entities
People
- Joseph B. Long
Organizations
- Walter Reed Army Institute of Research