Most arthritis is chronic by the time a patient presents in the clinic, so a rodent model of chronic inflammatory joint pain was used to investigate the mechanisms which contribute to pain in human joints. Freund’s complete adjuvant (FCA)-induced unilateral arthritis of the rat knee joint is a well established model of arthritis, mimicking the histopathology, hyperalgesia and swelling of the joint as seen in the clinic. In vivo electrophysiology, behaviour and immunohistochemistry techniques were used to elucidate the role played by opioid receptors and their endogenous ligands, and also the voltage-gated sodium channels (VGSCs), in chronic inflammatory joint hypersensitivity. Results from the in vivo electrophysiology studies show that during the chronic phase of FCA-induced joint hypersensitivity there are functional opioid receptors present in the periphery and agonists at these receptors are able to attenuate nociceptive firing evoked by noxious mechanical von Frey filaments. Furthermore EM1 and morphine administered directly into the knee joint attenuate the FCA-induced joint hypersensitivity by activating opioid receptors located in the periphery. Immunohistochemical results showed that the number of primary afferent neurons expressing the VGSCs was upregulated during FCA-induced inflammation, which could account in some part for the increased neuronal hypersensitivity observed in chronic inflammatory joint pain. Future novel analgesics targeting opioid receptors and VGSCs in the periphery may facilitate the breakthrough of a novel potent analgesic drug without undesirable centrally mediated side-effects.