Clinicians at University College London have, this week, reported the unusual case of a 66-year-old woman in Scotland who feels virtually no pain as a result of a previously unknown mutation in fatty-acid amide hydrolase (FAAH) chromosomal region.
The patient presented with nil requirement for postoperative analgesia after a trapeziectomy, which normally a condition requiring significant analgesia in the post-operative period. She also experienced very little anxiety and fear.
Further investigations revealed a lifelong history of painless injuries, with frequent cuts and burns, which were observed to heal quickly.
The cause of the condition was found to be the co-inheritance of a microdeletion in dorsal root ganglia and brain-expressed pseudogene (FAAH-OUT), which was cloned from the FAAH chromosomal region; and a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity.
Circulating concentrations of anandamide and related fatty-acid amides (palmitoylethanolamide and oleoylethanolamine) that are all normally degraded by FAAH were significantly elevated in peripheral blood compared with normal control carriers of the hypomorphic single-nucleotide polymorphism.
The authors say the genetic findings and elevated circulating fatty-acid amides are consistent with a phenotype resulting from enhanced endocannabinoid signalling and a loss of function of FAAH.
They say the case suggests new routes to develop FAAH-based analgesia by targeting FAAH-OUT, which could significantly improve the treatment of postoperative pain and potentially chronic pain and anxiety disorders.