Is there a role for paracetamol in evoked dysesthesia?

This continues focus on the cannabinoid receptors CB1 and CB2. You may think of them as interchangeable with VR-1.


The Canadians have been doing some interesting work on peripherhal neuropathy with paracetamol, which is also called acetominophen.

First, Guindon et al in Eur J Pharmacol. 2007 Jul 30;568(1-3):173-6 showed that a synthetic cannabinoid, named WIN 55 212-2, could perform preemptive blockade of peripheral neuropathic pain, BOTH mechanical allodynia (pain from what should not be painful ie touch) AND thermal hyperalgesia (lowered threshold for heat pain) were benefitted.

This has now been followed up with the demonstration by Dani, et al in Eur J Pharmacol. 2007 Jul 13, that parcetamol injections can also hit neuropathic pain. Equally interesting was the finding that blockade of the cannabinoid-1 and cannabinoid-2 receptors abolished the paracetamol effects.

Accompanying this is the finding by Guindon in Neuropharmacology. 2006 Jun;50(7):814-23 that injection of anandamide can also block peripheral neuropathic pain. NSAID’s work by blocking fatty acid maide hydrolase (FAAH)–see prior article on FAAH at this site. FAAH is the enzyme responsible for the production of anandamide. The effects of anandamide could be eliminated by blockage of cannabinoid-1 receptor, but NOT the cannabinoid-2 receptor.

In the second prior article at this site, we explain how anandamide, a relatively weak agent can have potent effects via the purine receptors.

Systemic cannabinoids, (marijuana) have undesirable central effects. However, it appears possible that peripheral neuropathy may be block by local blockers of cannabinoids, with no or relatively little central effect.

What good is this to central pain sufferers. This has not yet been investigated. Scientists are slowly beginning to segregate information about spontaneous burning dysesthesia, which probably results from the effects of body heat on purine receptors (see prior article on Burning up at normal temperature); and EVOKED burning dysesthesia, which is the real killer–the worst pain imaginable in severe cases. If the evoked component could be eliminated, many central pain sufferers would find life tolerable. The spontaneous dysesthesia operates at about the level of a sunburn, and bad as this is, it is tolerable. Since evoked pain requires some sort of stimulus, typically at the peripherae, it seems hopeful that if the peripheral nervous system can be desensitized, the elicited pain of light touch, mechanical allodynia, and perhaps even the thermal hyperalgesia could be treated.

We apologize for not having specific information before we bring this idea up, but we include the above to give hope to the suffering. We also bring it up as one more illustration of how money could be appropriately spent on basic pain research, to find pehaps a super acetominophen with a little molecular experimentation, which could be used topically. Cautio is in order for any long term use, since NSAIDs and some other similar medicines overwhelm and damage the kidney over time.

As time passes, more and more evidence points to the fact that the opiates simply do not cut it. Beside the fact opiates simply don’t work for most severe Central Pain, the literature are in agreement on undesirable effects, including addiction, and depression of the immune system by certain, common opioids.

Tolerance is also a problem for opiates with patients whose doses approach truly awesome levels after time, leading to physicians who feel they can no longer treat these individuals. Detoxification with some drugs, such as buprenorphine, can be performed and the whole process started over, but it is past the point where we can intelligently rely on opiates alone to treat central pain. It has never been absolutely clear that they are doing much more than mere sedation in CP. Still, we do get reports in the survey that opiates are actually stopping central pain. However, these reports almost never give sufficient information to be sure that the pain is neuropathic and not mechanical. Thus, the need for a vocabulary. Other avenues than opiates MUST be investigated.