Expression patterns and behavioral effects of conopressin and APGWamide in the nudibranch Berghia stephanieae.

The highly conserved oxytocin/vasopressin family of nonapeptides plays many roles across the animal kingdom, from osmoregulation to reproductive physiology. We investigated the expression patterns and pharmacological effects of the gastropod ortholog of this peptide, conopressin, along with another peptide involved in gastropod reproduction, APGWamide, in the nudibranch Berghia stephanieae. A brain transcriptome was used to identify and annotate the gene sequences for the peptides and one conopressin receptor. In-situ hybridization chain reaction showed that many neurons in the brain expressed these peptides. However, the peptide genes were co-expressed by only three neurons, which were in the right cerebral ganglion, the same side on which the reproductive organs are located. A conopressin receptor (BSCPR1) was expressed in a prominent population of APGWamide expressing neurons. Placing animals in a solution containing the APGWamide peptide caused minimal behavioral changes. However, exposure to conopressin reduced locomotion, increased gut contractions, and caused voiding at high concentration. The genes for these peptides and BSCPR1 were expressed in cells in the digestive system. BSCPR1 was also expressed by a line of neurons on the anterior portion of the radula and would be contacted during feeding. APGWamide-expressing neurons were found in the genital ganglion. All three genes expressed in cells on sensory appendages. These results are consistent with the conopressin playing a variety of roles in the brain and the body and being involved in both reproduction and digestion. This study sheds light on the function of this ancient nonapeptide in a new-to-neuroscience invertebrate species.

Trends in Gabapentin and Pregabalin Prescribing in a Tertiary Pediatric Medical Center.

OBJECTIVES: Analgesic medications are commonly prescribed in pediatrics, with prescribing practices frequently extrapolated from adult trials. Gabapentinoids (gabapentin and pregabalin) are widely used as analgesics but are labeled in pediatrics only for epilepsy. We aim to (1) define trends in pediatric gabapentinoid prescribing (label and off-label) over 7 years, and (2) evaluate use in chronic pain clinic (CPC) patients during 2018. METHODS: Retrospective data from a tertiary-care pediatric hospital were collected between 2013 and 2019. Annual numbers of gabapentinoid prescriptions were stratified by prescriber specialty. Additional information about gabapentinoid prescribing in the CPC was manually collected from initial clinic notes in 2018. RESULTS: There were 15 808 outpatient prescriptions for gabapentinoids among 5172 patients over 7 years. Of these, 93% were gabapentin and 7% were pregabalin. Numbers of patients receiving gabapentin and pregabalin prescriptions increased by 1.4- and 1.3-fold, respectively, between 2013 and 2019. Few prescriptions were done for patients with a previous epilepsy diagnosis (in 2019, 16% for gabapentin and 13% for pregabalin). Approximately 28% of 650 CPC new patients were prescribed gabapentin or pregabalin before referral. Among those, 44% had discontinued the medication because of adverse events (35%), inefficacy (46%), or both (5%). Most side effects reported were mild to moderate. Diagnoses at first visit were diverse, not limited to neuropathic pain conditions, and did not differ between patients receiving or not receiving gabapentinoid prescriptions. CONCLUSIONS: In our hospital, gabapentinoids are commonly prescribed off-label for diverse indications, including chronic pain. Future research is needed to evaluate gabapentinoid efficacy in these indications.