Background Splinting is a quite common intervention for the first carpometacarpal (CMC) osteoarthritis, however, underlying mechanisms of biomechanical and analgesic effects has not been fully investigated. The aim of this study was to develop an experimental basal thumb pain model and to elucidate the effects of CMC splinting on the pain profile and motor function. Methods In 14 healthy subjects, experimental basal thumb pain was induced by hypertonic saline injection into the dorsal radial ligament located on base of the first metacarpal bone. Isotonic saline was injected contralaterally as a control. Two experimental sessions with or without CMC splinting were conducted. Before, during and after injections, tip pinch strength was measured and surface electromyography of the abductor pollicis brevis (APB), first dorsal interosseous (FDI) and extensor pollicis longus (EPL) during tip pinch were evaluated in each session. Results Hypertonic saline induced significantly greater pain compared with baseline and isotonic saline (p < 0.01). Following hypertonic saline injection, the tip pinch strength decreased compared with baseline, concomitant with reduction of electromyographical activity of APB and FDI, but not of EPL (p < 0.05). The CMC splinting significantly improved the experimental pain, loss of pinch strength and inhibited intrinsic muscle activity compared with bare hand (p < 0.05). Conclusions A novel experimental model mimicking the first CMC joint pain was developed. The CMC splinting relieved the basal thumb pain and augmented pinch strength as well as intrinsic muscle activity. This study provides new insights into the pain relief and pinch strength improvement by splinting for painful CMC joint disorders. Significance Newly developed experimental basal thumb pain model decreased tip pinch strength approximately 50%, concomitant with the reduction of intrinsic muscle activities. Splinting for the first carpometacarpal joint significantly improved experimental pain, loss of pinch strength and inhibited intrinsic muscle activity compared with bare hand.