Ferulic acid dimer as a non-opioid therapeutic for acute pain.

purposeSearch for alternate pain medications has gained more importance in the past few years due to adverse effects associated with currently prescribed drugs including nervous system dysfunction with opioids, gastrointestinal discomfort with nonsteroidal anti-inflammatory drugs, and cardiovascular anomalies with cyclooxygenase-2 (COX-2) inhibitors. Phytomedicine has been explored for the treatment of pain, as these have been used for generations in regional communities and tend to lack major side effects in general. One such phytomedicine, incarvillateine (INCA), derived from the Chinese herb MATERIALS AND

methodsDimers of cinnamic acid (INCA analogs) were synthesized using cavitand-mediated photodimerization (CMP) method, which utilizes a macromolecule (γ-cyclodextrin) to control excited state reactivity of photoactive compounds. Acute pain response was assessed by using formalin-induced licking behavior in hind paw of mice, and neurologic function was monitored through locomotor activity, mechanical hyperalgesia, and thermal sensitivity upon administration of test compound. For mechanistic studies, binding to adenosine receptor was determined by using computer modeling.

resultsFerulic acid dimer (FAD), which has the same chemical functionalities on the aromatic ring as INCA, showed significant suppression of formalin-induced acute pain. Antinociceptive effect was observed primarily in the inflammatory phase, and no apparent behavioral changes related to the nervous system were noticeable. Inhibition of opioid receptor did not reverse antinociceptive response, and modeling data suggest adenosine 3 receptor binding.

conclusionFAD (INCA analog) shows potent nonopioid antinociceptive action mediated predominantly through