Cross-talk between Human Spinal Cord µ-opioid Receptor 1Y Isoform and Gastrin-releasing Peptide Receptor Mediates Opioid-induced Scratching Behavior.

BACKGROUND: Although spinal opioids are safe and effective, pruritus is common and distressing. The authors previously demonstrated in mouse spinal cord that interactions between µ-opioid receptor isoform 1D and gastrin releasing peptide receptor mediate morphine-induced scratch. The C-terminal of 1D inhibits morphine-induced scratch without affecting analgesia. The authors hypothesize that human spinal cord also contains itch-specific µ-opioid receptor isoforms which interact with gastrin releasing peptide receptor. METHODS: Reverse transcription polymerase chain reaction was performed on human spinal cord complimentary DNA from two human cadavers. Calcium responses to morphine (1 µM) were examined using calcium imaging microscopy on human cells (HEK293) coexpressing gastrin releasing peptide receptor and different human µ-opioid receptor isoforms. The authors assessed morphine-induced scratching behavior and thermal analgesia in mice following intrathecal injection of morphine (0.3 nmol) and a transactivator of transcription peptide designed from C-terminal sequences of 1Y isoform (0, 0.1, and 0.4 nmol). RESULTS: The authors demonstrated 1Y expression in the spinal cord dorsal horn. Morphine administration evoked a calcium response (mean ± SD) (57 ± 13 nM) in cells coexpressing both gastrin releasing peptide receptor and the 1Y isomer. This was blocked by 10 µM naltrexone (0.7 ± 0.4 nM; P < 0.0001), 1 µM gastrin-releasing peptide receptor antagonist (3 ± 2 nM; P < 0.0001), or 200 µM 1Y-peptide (2 + 2 nM; P < 0.0001). In mice, 0.4 nmol 1Y-peptide significantly attenuated morphine-induced scratching behaviors (scratching bouts, vehicle vs. 1Y-peptide) (92 ± 31 vs. 38 ± 29; P = 0.011; n = 6 to 7 mice per group), without affecting morphine antinociception in warm water tail immersion test (% of maximum possible effect) (70 ± 21 vs. 67 ± 22; P = 0.80; n = 6 mice per group). CONCLUSIONS: Human µ-opioid receptor 1Y isomer is a C-terminal splicing variant of Oprm1 gene identified in human spinal cord. Cross-talk between 1Y and gastrin releasing peptide receptor is required for mediating opioid-induced pruritus. Disrupting the cross talk may have implications for therapeutic uncoupling of desired analgesic effects from side effects of opioids.

Assessment for additional spinal trauma in patients with cervical spine injury.

An institutional review board-approved 8-year retrospective trauma registry analysis of cervical spine injuries (CSIs) was done in a Level 1 trauma center. This analysis includes 129 CSI patients (1.3% of trauma admissions). Cervical spine radiographs diagnosed injuries in 71 per cent of CSI patients. Cervical spine radiographs were false negative in 29 per cent of patients, who were found to have CSI on spine CT. Spine CT had 98 per cent sensitivity and detected 45 per cent additional injuries in cervical spine radiograph-positive patients. Spine CT scans were false negative in two patients with soft tissue injury. Cervical spine fractures were isolated in 45 per cent (n = 58) and multilevel in 55 per cent (n = 71) with contiguous fractures in 43 per cent (n = 55) of patients. Injuries involved two adjoining vertebrae in 38 patients and three or more adjoining vertebrae in 7 patients. C1-2 and C5-6 comprised 26 per cent and 20 per cent of all contiguous fractures. The least common was C7-T1, diagnosed in 2 per cent. The most common contiguous fractures were C1-2 in the elderly and C5-6 in children, comprising half of contiguous cervical injuries in the respective age groups. There were 26 (20.2%) noncontiguous injuries: 15 cervical and 11 cervicothoracolumbar. Multiple regions of the vertebral column were involved in 7.8 per cent of CSI patients. Spine CT is the preferred modality to assess CSI. Injuries were isolated in 45 per cent and were multilevel in the remaining CSI patients. Contiguous and noncontiguous injuries involving the cervical and thoracolumbar spine are common. Assessment of the entire spinal column should be done in patients with CSI.

Treatment of Refractory Status Epilepticus with Vagus Nerve Stimulator in an Elderly Patient.

BACKGROUND: One of the risks of a traumatically induced intracranial bleed is development of new onset seizures. Rarely would these seizures progress to status epilepticus (SE) or refractory SE. There is a lack of literature on the use of a vagus nerve stimulator in these situations in older adults. CASE DESCRIPTION: We present a 67-year-old patient who developed refractory status epilepticus within days after evacuation of a right-sided spontaneous subdural hematoma. He was refractory to multiple antiepileptic agents and phenobarbiturate- and propofol-induced coma. He then underwent a left vagus nerve stimulator (VNS) implantation. Within a few days of implantation, he improved dramatically. Within 2 weeks of VNS implantation, he was neurologically intact and was transferred to an inpatient rehabilitation facility. Within a short time thereafter, he was fully functional and able to take care of all of his activities. CONCLUSIONS: A vagus nerve stimulator should be considered in cases of refractory status epilepticus, regardless of age. Excellent outcome can be achieved even if a short course of medication-induced coma is unsuccessful.