Polyamine-free Diet to Prevent Post Surgery Hyperalgesia

Overview

After surgery, sensitization and hyperexcitability of central nervous system result in acute and long lasting postoperative pain. It has been shown that N-methyl-D-aspartate (NMDA) receptors antagonist (such as ketamine) prevent this adverse neuroplasticity and potentiate analgesic drugs efficacy. Polyamines (putrescine, spermidine, spermine) are essential components of cells functioning and are also known as allosteric modulators of NMDA receptors. In animal studies, polyamine-free diet has confirmed these antinociceptive properties. This research aims at evaluating anti hyperalgesic properties of polyamine-free diet in women operated on breast cancer versus kétamine

This multicentric, single blind study will enrol 160 women (18-75 years old) operated on tumorectomy and adenectomy (T1, T2, T3, N0, N1, M0) for breast cancer. Patients will be randomly assigned in a 2x2 factorial plan : Group 1 = control (n = 40) ; group 2 = ketamine group administered during and 48 hours after a standardized anesthesia (n = 40) ; group 3 = polyamine-free diet, 1 week and 72 hours after surgery (n = 40) ; group 4 : ketamine + polyamine-free diet (n = 40). The amount of morphine for the 24 first postoperative hours will be compared between each group as well as pain score, allodynia (Von Frey filaments) and hyperalgesia (algometer). Chronic pain occurrence (post-mastectomy pain syndrome) will be evaluated at 3 and 6 months using adequate questionnaire ( analgesic scale). Diet observance will be controlled preoperatively by a dosage of polyamines in circulating red cells blood. Polyamines deprivation and ketamine ability to reduce postoperative pain will be compared (isobolographic method). Anti-hyperalgesic properties of ketamine have already been demonstrated in urologic, orthopaedic and abdominal surgery. In case of additive or synergistic effect of a polyamine deprivation such a strategic could be helpful to achieve better postoperative rehabilitation in reducing chronic pain after surgery.