A review of pinealectomy-induced melatonin-deficient animal models for the study of etiopathogenesis of adolescent idiopathic scoliosis

Abstract

Adolescent idiopathic scoliosis (AIS) is a common orthopedic disorder of unknown etiology and pathogenesis. Melatonin and melatonin pathway dysfunction has been widely suspected to play an important role in the pathogenesis. Many different types of animal models have been developed to induce experimental scoliosis mimicking the pathoanatomical features of idiopathic scoliosis in human. The scoliosis deformity was believed to be induced by pinealectomy and mediated through the resulting melatonin-deficiency. However, the lack of upright mechanical spinal loading and inherent rotational instability of the curvature render the similarity of these models to the human counterparts questionable. Different concerns have been raised challenging the scientific validity and limitations of each model. The objectives of this review follow the logical need to re-examine and compare the relevance and appropriateness of each of the animal models that have been used for studying the etiopathogenesis of adolescent idiopathic scoliosis in human in the past 15 to 20 years.

Figure 1

Structure of melatonin.

Figure 2

Pinealectomy performed on a three-day-old chick. (A) Under isoflurane inhalation, chicken at three days post-hatching was subjected to general anesthesia for pinealectomy (PINX); and (B–D) The back of the cranium was cut open and the pineal gland was removed.

Figure 3

Occurrence of scoliosis in Kamei chickens. Unisex local bred Kamei chickens were pinealectomized (PINX) three days after hatching. X-ray taken thirteen days after the operation revealed a development of spinal curvature (encircled in red). At 34 days post-operatively, the chickens were sacrificed and autopsy was conducted to evaluate the incidence of scoliosis. All of the chickens in the PINX group demonstrated scoliosis (n = 7), while no scoliosis was detected in the sham-operated control group (n = 6).