Instilled or Injected Purified Natural Capsaicin Has No Adverse Effects on Rat Hindlimb Sensory-Motor Behavior or Osteotomy Repair

A novel formulation of > or = 98% pure capsaicin (4975) is currently undergoing clinical investigation using novel routes of delivery to provide selective analgesia lasting weeks to months with a single dose. We conducted this study to assess the safety and effects of instilled and injected 4975 in rat models of wound healing osteotomy repair and sensory-motor nerve function. Adult male and female Sprague-Dawley rats were used. To assess the effects of 4975 on nerve or muscle, 0.0083 or 0.025 mg 4975 or vehicle (25% polyethylene glycol-300) was applied to exposed sciatic nerve, or 0.1 mg 4975 or vehicle was injected into the surrounding muscle (Group 1). To assess the effect of 4975 on bone healing, an osteotomy was made in one femur and 0.5 mg of 4975 or vehicle was instilled into the site (Group 2). Behavioral testing was performed on both groups of rats and histological evaluation of the sciatic nerve, and surrounding soft tissue and bone was done at days 3, 14, and 28 after surgery. Femurs from osteotomy rats were assessed using peripheral quantitative computed tomography and biomechanical testing. Standard statistical tests were used to compare groups. Rats with direct application of 4975 to the sciatic nerve and surrounding muscle were no different from the controls in nociceptive sensory responses (F = 0.910, P = 0.454), grip strength (F = 0.550, P = 0.654), or histology of the muscle or sciatic nerve. In osteotomy rats, there were no statistical differences between 4975 and vehicle-treated rats for bone area (H = 2.858, P = 0.414), bone mineral content (F = 0.945, P = 0.425), or bone mineral density (F = 0.87, P = 0.462) and no difference in soft tissue healing. There were neither differences in bone stiffness (F = 1.369, P = 0.268) nor were there noticeable differences in the macro- or microscopic appearance of the right femur osteotomy healing site and surrounding soft tissues between the control group and the 4975-treated animals. A single, clinically relevant application of instilled or injected 4975 has no observable adverse effect on wound and bone healing after osteotomy or on the structural integrity of exposed muscle and nerve.