An endocannabinoid mechanism for stress-induced analgesia

  title={An endocannabinoid mechanism for stress-induced analgesia},
  author={Andrea G. Hohmann and Richard Lee Suplita and Nathan M. Bolton and Mark H. Neely and Darren Fegley and Regina A. Mangieri and Jocelyn F Krey and J. Michael Walker and Philip V. Holmes and Jonathon D. Crystal and Andrea Duranti and Andrea Tontini and Marco Mor and Giorgio Tarzia and Daniele Piomelli},
Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB1 receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous… 
The endocannabinoid system and pain.
The roles of anandamide and 2-arachidonoylglycerol, released under physiological conditions, in modulating nociceptive responding at different levels of the neuraxis will be emphasized in this review.
Endocannabinoid mechanisms of pain modulation
This review will provide a comprehensive evaluation of the roles of the endocannabinoids 2-arachidonoyl-glycerol and anandamide in stress-induced analgesia and provide a functional framework with which to understand the roles in nociceptive processing at the supraspinal level.
Stress‐induced analgesia in mice: evidence for interaction between endocannabinoids and cholecystokinin
Testing whether abolishing the endogenous CCK tone might influence the cannabinoid‐mediated form of SIA suggested that CCK, through CCK2 receptors, modulates the action of endocannabinoids.
The Role of the Brain's Endocannabinoid System in Pain and Its Modulation by Stress.
Targeting the cannabinoid system for pain relief?
  • L. Chiou, S. Hu, Y. Ho
  • Biology, Chemistry
    Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists
  • 2013
Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids
  • M. Hill, B. McEwen
  • Biology
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 2010


Modulation of anxiety through blockade of anandamide hydrolysis
The results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy.
Pain modulation by release of the endogenous cannabinoid anandamide.
Findings indicate that the endogenous cannabinoid anandamide plays an important role in a cannabinergic pain-suppression system existing within the dorsal and lateral PAG, and may have relevance for the treatment of pain, particularly in instances where opiates are ineffective.
A second endogenous cannabinoid that modulates long-term potentiation
2-AG activates neuronal cannabinoid receptors as a full agonist, and prevents the induction of long-term potentiation at CA3–CA1 synapses, indicating that 2-AG is a second endogenous cannabinoid ligand in the central nervous system.
An analgesia circuit activated by cannabinoids
It is shown that a brainstem circuit that contributes to the pain-suppressing effects of morphine is also required for the analgesic effects of cannabinoids, and that cannabinoids are indeed centrally acting analgesics with a new mechanism of action.
The Many Possible Roles of Opioids and Related Peptides in Stress‐Induced Analgesia a
The role of opioids in pain regulation in general and in stress-induced analgesia in particular are discussed, and the importance of understanding the cell biology and its regulatory dynamics in attempting to link these mechanisms is conveyed.
Reduction of stress‐induced analgesia but not of exogenous opioid effects in mice lacking CB1 receptors
The results indicate that CB1 receptors are not involved in the antinociceptive responses to exogenous opioids, but that a physiological interaction between the opioid and cannabinoid systems is necessary to allow the development of opioid‐mediated responses to stress.
Brain monoglyceride lipase participating in endocannabinoid inactivation
The results suggest that hydrolysis by means of MGL is a primary mechanism for 2-AG inactivation in intact neurons, and not on the accumulation of anandamide, another endocannabinoid lipid.
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice.
Most, but not all, CNS effects of Delta9-THC are mediated by the CB1 receptor, which accounts for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications.
Actions of cannabinoids on membrane properties and synaptic transmission in rat periaqueductal gray neurons in vitro.
It is suggested that cannabinoids act via CB(1) receptors to inhibit GABAergic and glutamatergic synaptic transmission in rat PAG, although the efficacy of endogenous cannabinoids is likely to be limited by uptake and breakdown.