In Vitro Growth Effects of Morphine and Naloxone on Various Head and Neck Squamous Cell Cancer Cell Lines

Understanding the potential effects of mu-agonism and antagonism on cancer cells is important for the perioperative physician. Previous studies suggest some tumor cells may have altered growth with mu-agonism or antagonism. This study investigates the effects of morphine (mu-agonist) and naloxone (mu-antagonist) in head and neck tumor cell lines (laryngeal squamous cell carcinoma (SCC), lateral tongue SCC and base of tongue SCC). Morphine showed no significant effect on tumor cell growth. Naloxone showed significant inhibition of growth in laryngeal SCC, but not in lateral or base of tongue SCC.

Interleukin-6 is differently modulated by central opioid receptor subtypes

The central endogenous opioid system is involved in the modulation of interleukin (IL)-6, an inflammatory cytokine that plays a major role in the acute phase response. The present study evaluates whether specific opioid receptor subtypes are selectively involved in this immunomodulatory action. IL-1 beta was administered either intracerebroventricularly or intraperitoneally at the dose of 400 ng to rats pretreated with the mu-antagonist beta-funaltrexamine, the delta-antagonist naltrindole, or the kappa-antagonist nor-binaltorphimine, each at the doses of 1, 10, and 100 micrograms/rat intracerebroventricularly. Serum IL-6 levels were measured 2 h later. The results show that mu-receptor blockade increases, whereas delta-receptor blockade decreases IL-6 induction, suggesting that the fine tuning exerted by opioids on the immune system may be achieved through a balance of opposing effects. Moreover the three antagonists affect IL-6 induction by central and peripheral IL-1 beta with a similar pattern, indicating that the brain endogenous opioid system plays a general role in the regulation of this cytokine.

Mu- vs. delta-opioid influence on respiratory and sleep behavior during development

The role of mu- vs. delta-opioid receptors in modulating cardiorespiratory and sleep/wake behavior was studied in sixteen 4- to 11-, and 26- to 33-day-old chronically instrumented piglets. Each underwent 1.5-h recordings of sleep/wake state, diaphragmatic and posterior cricoarytenoid electromyogram (EMGdi, EMGpca), heart rate, and arterial pressure, pH, and gas tensions, before and after either naltrexone (2 mg/kg i.v.), a predominantly mu antagonist, or naltrindole (4 mg/kg i.v.), a specific delta antagonist. In younger piglets, 1) naltrindole, but not naltrexone, decreased percent of time spent in active and quite sleep and increased that in wakefulness, and 2) naltrexone, but not naltrindole, increased respiratory frequency, decreased the duration of EMGdi and EMGpca activity, and increased initial summed EMGdi activity, all independently of state. Older piglets exhibited 1) increased arousal with both drugs and 2) weaker stimulation of respiratory timing and no stimulation of EMGdi or EMGpca with naltrexone and enhanced EMGpca activity with naltrindole during transitional sleep only. Thus, in early neonatal life, delta-opioid systems modulate sleep/wake behavior, whereas mu systems modulate respiration. With age, these influences change and become less specific.