Supraspinal actions of nociceptin/orphanin FQ, morphine and substance P in regulating pain and itch in non-human primates.

BACKGROUND AND PURPOSE: Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects of centrally administered ligands on regulating pain and itch in non-human primates. In particular, nociceptive thresholds affected by intracisternal N/OFQ were compared with those of morphine and substance P, known to provide analgesia and mediate hyperalgesia, respectively, in humans. EXPERIMENTAL APPROACH: Intrathecal catheters were installed to allow intracisternal and lumbar intrathecal administration in awake and unanaesthetized rhesus monkeys. Nociceptive responses were measured using the warm water tail-withdrawal assay. Itch scratching responses were scored from videotapes recording behavioural activities of monkeys in their home cages. Antagonist studies were conducted to validate the receptor mechanisms underlying intracisternally elicited behavioural responses. KEY RESULTS: Intracisternal morphine (100 nmol) elicited more head scratches than those after intrathecal morphine. Distinct dermatomal scratching locations between the two routes suggest a corresponding activation of supraspinal and spinal µ receptors. Unlike intracisternal substance P, which induced hyperalgesia, intracisternal N/OFQ (100 nmol) produced antinociceptive effects mediated by NOP receptors. Neither peptide increased scratching responses. CONCLUSIONS AND IMPLICATIONS: Taken together, these results demonstrated differential actions of ligands in the primate supraspinal region in regulating pain and itch. This study not only improves scientific understanding of the N/OFQ-NOP receptor system in pain processing but also supports the therapeutic potential of NOP-related ligands as analgesics.

Naturally occurring extracellular matrix as a scaffold for musculoskeletal repair.

The use of naturally occurring extracellular matrix materials as scaffolds for the repair and regeneration of tissues is receiving increased attention. The present study evaluates the use of the extracellular matrix derived from porcine small intestinal submucosa as a scaffold for anterior cruciate ligament replacement in a goat model. Sixty healthy adult female goats were divided into two equal groups of 30 each. The right anterior cruciate ligament of each goat was removed surgically and replaced with either a patellar tendon autograft or a small intestinal submucosa anterior cruciate ligament scaffold. Three animals from each group were sacrificed at 6 weeks, 3 months, 6 months, and 1 year after surgery and grafts were harvested for histopathologic examination. Six animals from each group were sacrificed immediately after surgery, 3 months, and 1 year after surgery and the grafts were harvested for biomechanical testing. There was no evidence for an adverse clinical response to the xenogeneic small intestinal submucosa scaffold. Anterior drawer values were not different between the two groups at any point. The failure force of the patellar tendon autograft increased from 253 N at Time 0 to 879 N at 12 months. The failure force for the small intestinal submucosa repair device was 721 N at Time 0, decreased to 293 N at 3 months, followed by an increase to 706 N at 12 months. Histopathologic analysis showed a mixed inflammatory cell presence within the small intestinal submucosa scaffold including macrophages and lymphocytes in the early months after surgery. The inflammatory cells disappeared in the later stages of remodeling and the histologic appearance of the small intestinal submucosa remodeled grafts and the patellar tendon autografts were indistinguishable at 12 months. Xenogeneic small intestinal submucosa holds promise as a resorbable bioscaffold for anterior cruciate ligament repair in the goat model.

A Survey of Tomatoes Home-Canned in Utah.

Sample jars of home-canned tomato products collected in Utah counties during the 1975 canning season were tested for pH, titratable acidity, vacuum, headspace and number of microorganisms. Each consumer was interviewed to determine the times and temperatures used to process each product. Three methods were used including waterbath, pressure canner and open kettle. Acidity was sufficient (< 4.6) in all samples to inhibit the growth of Clostridium botulinum with the exception of one sample (pH 6.8) containing excessive numbers of fungi. Four to five percent of the samples exhibited no vacuum after storage, contained microorganisms and were underprocessed.