This endogenous cannabinoid continues to be interesting.
It is always important to consider WHICH model of neuropathic pain is being studied before concluding that it would have broad application. Two common models are injection of carrageenan into the foot or a joint, and partial ligation of the sciatic nerve. These are, of course, models of peripheral neuropathy and NOT models of Central Pain. However, it is often true that something can be learned about central pain by watching responses in peripheral nerve injury.
A recent article in Time magazine claimed Alzheimer’s involves some element of inflammation and that Sativex may be useful in reducing such inflammmation. This is not a wild claim, since the cannabinoids have long been linked to inflammation, and also to pain.
We have written before about anandamide, which has been termed an endogenous cannabinoid, which means it is made by the body and also that it acts on at least one of the same receptors that cannabis acts on. There are two main ones, CB1 and CB2.
Anandamide moves from the space around cells, and is then degraded by fatty acid amide hydrolase (FAAH). Anything which inhibits or antagonizes FAAH should therefore accentuate the action of anandamide, which has an antihyperalgesic action.
Jayamanne et al in the British J. Pharm Dec 5, 2005, have noted that a blocker of all the cannabinoid receptors causes diminished motor function, but a selective blocker of FAAH reduces the thermal hyperalgesia but does not reduce the mechanical allodynia in the nerve ligation model. The pan-cannabinoid blocker reduced both types of pain, possibly because it reduces inflammation.
These studies on cannabinoids do not necessarily make a case for cannabinoid use, but they do illustrate the value of studying the CB1 and CB2 receptors and the behavior of fatty acids around the nerve cell. It is not unusual for different receptors to be acting on the same molecule, only at different spots. Studying the binding at these locations often gives hints at future therapeutic agents. Because fatty acids are so well known to be related to perineural acidosis, it is not surprising in the least that their degradation might have some antihyperalgesic activity. Their action is not the whole story, since acidification in the body involves a number of compounds, such as cytokines, prostaglandins, potassium, etc., apparently working in the aggregate in Central Pain.
