Mail-Back Envelopes for Retrieval of Opioids After Pediatric Surgery.

BACKGROUND: Opioid overprescription has the potential to lead to harmful medications remaining in homes and to a rise in accidental or deliberate ingestion by children and adolescents. Although methods for opioid disposal are available, many are costly or require greater than minimal effort for the patient. In this study, we used a mail-back return envelope to retrieve unused opioids after ambulatory pediatric surgery. METHODS: This feasibility study was performed to assess the rate of opioid return by using a mail-back envelope for children ages 0 to 18 prescribed opioids after outpatient surgery. Participants were provided a return envelope as well as instruction on the dangers of opioids in the home. Our primary outcome was to assess the absolute percent return rate through the use of a mail-back envelope. RESULTS: Between November 2017 and October 2018, we identified 355 patients, of whom 331 were included in the analysis. In total, 64 (19.3%) returned opioids. In total, >2000 mL of liquid opioids and >250 tablets or nearly 3000 mg of oral morphine equivalents were removed from the homes of the 64 participants. Of those patients returning unused medications, the median rate of return was 58% (interquartile range = 34.7%-86.1%) of the written prescription. CONCLUSIONS: The findings suggest that providing a free mail-back return envelope is a suitable way to remove unused opioids from the home after pediatric surgery. Additional research is needed to identify barriers to return of unused medications.

Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury.

Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is described by the region affected: above-level, at-level and below-level pain occurs in dermatomes rostral, at/near, or below the SCI level, respectively. People with SCI and rodent models of SCI develop above-level pain characterized by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain are unknown and the goals of this study were to elucidate components contributing to the generation of above-level CNP. Following a thoracic (T10) contusion, forelimb nociceptors had enhanced spontaneous activity and were sensitized to mechanical and thermal stimulation of the forepaws 35 days post-injury. Cervical dorsal horn neurons showed enhanced responses to non-noxious and noxious mechanical stimulation as well as thermal stimulation of receptive fields. Immunostaining dorsal root ganglion (DRG) cells and cord segments with activating transcription factor 3 (ATF3, a marker for neuronal injury) ruled out neuronal damage as a cause for above-level sensitization since few C8 DRG cells expressed AFT3 and cervical cord segments had few to no ATF3-labeled cells. Finally, activated microglia and astrocytes were present in thoracic and cervical cord at 35 days post-SCI, indicating a rostral spread of glial activation from the injury site. Based on these data, we conclude that peripheral and central sensitization as well as reactive glia in the uninjured cervical cord contribute to CNP. We hypothesize that reactive glia in the cervical cord release pro-inflammatory substances which drive chronic CNP. Thus a complex cascade of events spanning many cord segments underlies above-level CNP.

Mechanism by which peripheral galanin increases acute inflammatory pain.

Galanin (GAL) is a neuropeptide involved in pain transmission. Intraplantar GAL at low doses enhances capsaicin (CAP)-induced pain behaviors in rat, suggesting an excitatory role for GAL under acute inflammatory conditions. The mechanisms underlying this pro-nociceptive action have not yet been elucidated. Thus, the present study investigated the role of protein kinase C (PKC) in the GAL enhancement of CAP-induced inflammatory pain. Ipsilateral, but not contralateral, calphostin C, a PKC inhibitor, blocked GAL-induced potentiation of CAP-evoked inflammatory pain in a dose-dependent fashion. Peripheral activation of PKC using the phorbol ester phorbol-12-myristate-13-acetate (PMA) mimicked the pro-nociceptive effect of GAL. These results suggest that GAL enhances acute inflammatory pain through activation of PKC intracellular pathways.

Pro-nociceptive role of peripheral galanin in inflammatory pain.

We investigated the peripheral function of galanin (GAL) in capsaicin (CAP)-induced inflammatory pain. Intraplantar GAL (0.1 ng/microl) alone does not produce nociceptive behaviors. However, ipsilateral but not contralateral GAL at low doses (0.1 ng/microl) significantly increases CAP-evoked nociceptive behaviors approximately twofold. This effect is attributed to activation of peripheral GAL receptor 2 (GalR2) because a selective GalR2 agonist (AR-M1896) mimics the pro-nociceptive actions of GAL. Recording from nociceptors confirms that GAL does not modify activity of nociceptors but markedly enhances CAP-induced excitation of these fibers. CAP produces a discharge rate of 0.15+/-0.05 impulses/s which increases to 0.54+/-0.17 impulses/s following CAP+GAL. Immunohistochemical studies indicate GalR2 are highly expressed (65.8%) in L5 dorsal root ganglion (DRG) cells. Also, 44.5% GalR2-positive DRG neurons label for the capsaicin receptor (vanilloid receptor 1, VR1) while 61.7% of VR1-positive DRG neurons label for GalR2; 28.1% of total DRG neurons are double-labeled supporting the hypothesis that GAL-induced effects are mediated by GalR2 on capsaicin-sensitive primary afferents. Furthermore, 68.0% unmyelinated and 23.1% myelinated digital nerve axons label for GalR2, indicating the receptor is transported out to the periphery. Immunostaining for GAL peptide in digital nerves labels 46.4% unmyelinated and 27.1% myelinated axons, suggesting that afferents are a major source of ligand for peripheral GalR2. These results suggest that peripheral GAL has an excitatory role in inflammatory pain, likely mediated by peripheral GalR2 and that GAL can modulate VR1 function.