BACKGROUND AND AIMS: Congenital Insensitivity to Pain (CIP) predisposes to a range of articular problems. Knowledge of this condition’s genetic determinants has produced a huge interest in novel analgesics against Nav1.7 and NGFB. However, concerns have been raised due to adverse joint sequelae, such as rapidly progressive osteoarthritis in Tanezumab therapy. I studied the phenotypes of patients with  CIP to analyse the pattern of the articular consequences to extrapolate any side effects of long-term novel analgesic treatment in adults.

METHODS: I did a comprehensive Medline (via Ovid) search to identify all the relevant case reports since 1970. The papers were screened on Rayyan QCRI. The selected cases were analysed based on sex, age, articular/bone pathology location and mutated genes. 

RESULTS: 111 cases were identified (67 Male and 44 Female) with 56 NTRK1, one NGFB, one SCN9A, one SCN11A and one PRDM2 mutation. The reported mean age was 8.5 years (7.5 SD) for non-spinal articular pathology, while 29.3 years (7.5 SD, n=10) for spinal pathology. Hand and feet (52%), hip (20%), knee (19%) and elbow (6%) were commonly affected.

CONCLUSIONS: Articular pathology is common in CIP. Spine vs. non-spine joint pathology show a bi-modal distribution (spine in older patients). This suggests that novel analgesic therapy based on these targets should consider long-term spine injury as a side effect in adults.

ARTICULAR CONSEQUENCES OF A LIFE WITHOUT PAIN AND LESSONS FOR NOVEL ANALGESIA: A LITERATURE REVIEW AND ANALYSIS