Developmental pharmacology of opioids

Author(s):  
Gareth Hathway

Recognition of the need for alternative analgesic regimens for managing neonatal and childhood pain has led to a rich literature concerning the ways in which early life pain differs from that at older ages. As in adults, opiates are often considered the gold-standard analgesic class of drugs, of which morphine is the prototypical agent. There is a wealth of data detailing clinical observations, measurements, and interventions with regard to the use of opioids in treating pain in children. Studies in the early part of this century have highlighted that, in humans, age is an important factor that influences the morphine requirement of neonates following surgery, and dose requirements are influenced by both pharmacokinetic and pharmacodynamic factors. Laboratory studies have extended our understanding of changes within the peripheral and central nervous systems that underlie alterations in nociception in early life. This chapter will review what is currently known about the actions of opioids upon nociceptive and nociresponsive elements of the nervous system in early life, how they differ from adult responses, and ask whether manipulating endogenous opioid systems in early life may have consequences on neurodevelopment.

Author(s):  
Gareth J. Hathway

Recognition of the need for alternative analgesic regimens for managing neonatal and childhood pain has led to a rich literature concerning the ways in which early life pain differs from that at older ages. As in adults, opiates are often considered the gold standard analgesic class of drugs, of which morphine is the prototypical agent. There is a wealth of data detailing clinical observations, measurements, and interventions with regard to the use of opioids in treating pain in children. Studies in the early part of this century have highlighted that, in humans, age is an important factor that influences the morphine requirement of neonates following surgery; and dose requirements are influenced by both pharmacokinetic and pharmacodynamic factors. Laboratory studies have extended our understanding of changes within the peripheral and central nervous systems that underlie alterations in nociception in early life. This chapter will review what is currently known about the actions of opioids upon nociceptive and nociresponsive elements of the nervous system in early life, how they differ from adult responses, and ask whether manipulating endogenous opioid systems in early life may have consequences on neurodevelopment.


2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Carlyn C Zylstra ◽  
Lisa M Zelinski ◽  
Eunhee Chung ◽  
Yusuke Ohgami ◽  
Donald Y Shirachi ◽  
...  

1996 ◽  
Vol 1 (4) ◽  
pp. 207-211
Author(s):  
Perry N Fuchs ◽  
Bradley Kerr ◽  
Ronald Melzack

BACKGROUND:Several reports in the 1960s demonstrated that methotrimeprazine (MTMZ), a phenothiazine derivative, is effective for treating acute and chronic pain. Although MTMZ has received little attention in recent decades, the fact that it derives from a class of drugs usually associated with cognitive and emotional processes, rather than the traditional analgesics, makes it interesting as a potential source of information about the mechanisms of analgesia.OBJECTIVE:To explore the analgesic properties of MTMZ in a dose-related design in the formalin test, and to examine whether the lowest dose of MTMZ that produces analgesia will activate endogenous opioid systems.METHODS:The analgesic properties of three doses of MTMZ, compared with a saline control, were explored in male Sprague-Dawley rats using the formalin test. Sedative effects were studied by using the line-crossing test concomitantly with the formalin test.RESULTS:MTMZ had no effect during the first phase of formalin responding. During the second phase of the formalin test, MTMZ doses of 5.0 and 10.0 mg/kg produced a significant decrease in formalin responses. Sedative effects were observed at all doses, even though the dose of 2.5 mg/kg did not significantly decrease formalin responses compared with controls. Statistical analyses revealed no significant correlation between the degree of sedation and the degree of analgesia at any dose of MTMZ. The nonspecific opioid antagonist naloxone did not alter the analgesic effect of 5.0 mg/kg MTMZ, indicating that the mechanism of action is independent of endogenous opioid systems.CONCLUSION:MTMZ decreased responses in the formalin pain test in rats. Although the drug's sedative effects were apparent in the line crossing test, they were not significantly correlated with pain responses. These results suggest that the decrease in formalin responses might be due, in part at least, to the analgesic properties of MTMZ. The fact that MTMZ belongs to a class of drugs that is relatively unexplored in relation to pain and analgesia indicates a potential source for the development of new pharmacological agents for treating persistent pain. Furthermore, the nonopioid mechanism of action suggests that this agent may be useful when opioid medications are contraindicated.


Physiology ◽  
1996 ◽  
Vol 11 (5) ◽  
pp. 223-228 ◽  
Author(s):  
P Hoffmann ◽  
IH Jonsdottir ◽  
P Thoren

Many positive effects of exercise have been ascribed to the exercise-induced activation of endogenous opioid systems. The hypothesis that different opioid peptides and receptors are involved in the cardiovascular, behavioral, and analgesic responses and that opioid-mediated effects of muscle exercise are triggered by activation of mechanosensitive muscle nerve afferents is reviewed.


2002 ◽  
Vol 945 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Long-Chuan Yu ◽  
Jiang-Teng Lu ◽  
Yan-Hua Huang ◽  
Thomas Meuser ◽  
Christian Pietruck ◽  
...  

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