ABSTRACT
INTRODUCTION: Bupivacaine is one of the commonly used agents for spinal anaesthesia. Moreover, co-administration with morphine can likely increase its anti-nociceptive effect bringing about a reduction in the required dose of bupivacaine. Though this has been observed clinically, preclinical studies on the efficacy of this drug combination are lacking. METHODS: Sprague Dawley rats, previously implanted with intrathecal catheters, were administered either bupivacaine (30 mcg) or morphine (30 mcg) or both bupivacaine and morphine (15 mcg each). These doses were determined following prior evaluation of different doses of bupivacaine (3, 10 and 30 mcg). Rats were subjected to hind paw incision under isoflurane anaesthesia, 15 min after drug administration. Anti-nociception was evaluated by estimating mechanical allodynia in a fixed peri-incisional area using von Frey filaments. This was done 4 h after the incision. RESULTS: Both bupivacaine and morphine attenuated allodynia though morphine was more effective. Co-administration of both drugs at half the doses increased the antinociceptive effect of bupivacaine to the 30 mcg dose level. CONCLUSION: The underlying reason for this enhanced anti-nociception could be the different neural mechanisms responsible for anti-nociception. Local anaesthetics inhibit the generation of action potentials by blocking sodium channels whereas opioids like morphine act through G-protein coupled mu opioid receptor-linked closure of calcium channels in presynaptic terminals. In conclusion, the addition of morphine can facilitate bupivacaine's anti-nociceptive effect following intrathecal administration. This information could have clinical relevance in the treatment of postoperative pain.
ABSTRACT
Drug dependence associated with increased dopamine neurotransmission and neuroplastic changes is influenced by Dopamine transporters (DAT) which are modulated by genetic and epigenetic factors. This study assesses DAT availability in relation to the 40bp DAT1 VNTR (genetic) and DAT1 promoter methylation (epigenetic) changes in patients with alcohol dependence (AD) and opioid dependence (OD). A total of 60 subjects (n=20 each of AD, OD and controls) were recruited. SPECT/CT imaging using 99mTc-TRODAT-1 was performed for measuring striatal DAT availability and DNA screened to check DAT1promoter methylation and 40bp VNTR polymorphism. SPECT/CT imaging revealed significant decrease in DAT availability in the striatum and putamen and significant increase in DAT1 promoter methylation in AD compared to control and OD. The 40bp VNTR distribution was similar in all three groups with 10repeat and 9repeat alleles being the most common. The AD individuals with DAT1promoter methylation showed significantly lower TRODAT-1 uptake compared to the ones with no methylation. AD individuals homozygous for the 10repeat VNTR also showed reduced DAT availability. This is the first imaging study using 99mTc-TRODAT-1 from India documenting significantly reduced striatal DAT availability, increased DAT methylation and frequency of 10repeat individuals associated with decreased DAT availability in AD.
