Oxaliplatin and
paclitaxel are considered central components in the treatment of colorectal and
breast cancer, respectively. The development of neuropathy during chronic treatment represents the major dose-limiting side effect that leads to discontinuation or interruption of
therapies. The management of neuropathy is a challenge to individuate innovative therapeutic strategies based on new targets and correct routes of administration. We evaluated the
hypersensitivity reliever effect of different
opioid receptor agonists in rat models of
oxaliplatin and
paclitaxel-induced neuropathy. Compounds were spinally infused by intrathecal
catheter. In
oxaliplatin-treated rats, 0.3 nmol
morphine induced the reversion of the mechanical
hypersensitivity (Paw-pressure test),
nociceptin/orphanin FQ (N/OFQ; 0.3-3 nmol) significantly increased the pain threshold without reaching the values of the control animals. The
N/OFQ peptide (NOP) receptor full agonist
UFP-112 reverted pain threshold alterations at lower dosage (0.1 nmol) vs
morphine and N/OFQ, the partial agonist UFP-113 (0.1-1 nmol) was similar to N/OFQ. The higher efficacy of
morphine vs N/OFQ was highlighted also in
paclitaxel-treated rats. The mechanical
hypersensitivity was fully reverted by 0.1 nmol
UFP-112 and UFP-113. In conclusion, intrathecal μ
opioid peptide (MOP) and NOP receptor agonists relieved
chemotherapy-induced
neuropathic pain. The synthetic
peptides showed valuable potency and efficacy suggesting the NOP system as an exploitable target.