Evidences have shown that chemotherapeutics induce peripheral neuropathic pain, an hypersensitization of the conducting nerves characterized by shooting or burning sensation following gentle touch (which would not provoke pain in healthy individuals).
This condition is also said allodynia, described as a lower threshold to pain, which is often caused as a secondary symptoms to many illnesses, such as cancer, diabetes, multiple sclerosis but can also be caused by human intervention, due to medicines (like chemotherapeutics) or in post-op (i.e. dental surgery).
A pharmacological trick to eliminate THC side effects
It has been widely proved that activation of the CB1 receptors (Classic cannabinoid receptors) provides relief from pain.
However, direct activation at this receptor causes the psychotropic effects that have precluded Cannabis access to most Countries.
The laboratory of Dr Pertwee and colleagues have found an interesting alternative by the use of a method to overcome the side effects associated with THC.
They investigated a compound, GAT211, which modulates the activity at CB1 receptors allosterically; in other words, whilst the THC molecule binds directly to the receptor (think LEGO elements fitting perfectly into each other), GAT211 binds elsewhere on the surface of the receptor, inducing conformational changes in the receptors (said orthosteric binding).
Cannabinoid receptors, such as CB1, belong to a very large family of receptors that is called G-Protein Coupled Receptors (or GPCRs in short).
The mechanism of function of this receptor family requires a brief introduction in order to understand better GAT211 actions.
You can imagine the receptors (usually at the surface of cells) as door locks.
When the correct key (which in pharmacology is said ligand) is inserted in the receptor, a chain of events is triggered and many proteins get involved so that physiological effects take place.
Thus, GAT211 is capable to increase signals downstream from the receptors, causing physiological events, but to does not operate directly as a key-and-lock mechanism.