Comment: The presence of opioid receptors outside of the central nervous system is a well known fact, the significance of which is still being investigated. The endogenous opioid peptides (EOP) found in immune cells present in inflamed synovial tissue stress the EOP's role in inflammation. Most likely, up-regulation of peripheral opioid recepts during inflammation is counted by the delivery of EOP into the injured area by immune cells. The connection between immunological function and the intrinsic mechanism involved in pain inhibition merits future investigation. Another application of the “peripheral gate” pain control theory advocated by the authors could be the development of peripherally acting analgesic devoid of the adverse central effects exhibited by opioids.