TY - JOUR

T1 - Spinal neuronal correlates of tapentadol analgesia in cancer pain: A back-translational approach

AU - Falk, Sarah

AU - Patel, Ryan

AU - Heegaard, Anne-Marie

AU - Mercadante, Sebastiano

AU - Dickenson, Anthony H

PY - 2015

Y1 - 2015

N2 - BackgroundPain is a common and highly debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of multiple mechanisms including both inflammatory and neuropathic processes and also some unique changes. Strong opioids are a mainstay of treatments but side effects are problematic and can compromise optimal pain control. Tapentadol is a novel dual-action drug, both stimulating inhibitory μ-opioid receptors (MOR) and mediating noradrenaline reuptake inhibition (NRI) leading to activation of the inhibitory α-2 adrenoceptor. It has been demonstrated to treat effectively both acute and chronic pain. We here demonstrate the efficacy in a model of cancer-induced bone pain.MethodsMRMT-1 mammary carcinoma cells were inoculated into the tibia of 6-week-old rats and 2 weeks after, the neuronal responses to a wide range of peripheral stimulation were evaluated. The recordings were made from wide-dynamic range neurons in lamina V of the dorsal horn before and after administration of tapentadol as well as antagonists of the two mechanisms, naloxone or atipamezole.ResultsWe found marked inhibitions of the neuronal activity with efficacy against mechanical, thermal and electrically evoked activity following tapentadol administration. In addition, the effects of the drug were fully reversible by naloxone and partly by atipamezole, supporting the idea of MOR-NRI dual actions.ConclusionsThese findings add to the mechanistic understanding of cancer-induced bone pain and support the sparse clinical data indicating a possible use of the drug as a therapeutic alternative for cancer patients with metastatic pain complication.

AB - BackgroundPain is a common and highly debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of multiple mechanisms including both inflammatory and neuropathic processes and also some unique changes. Strong opioids are a mainstay of treatments but side effects are problematic and can compromise optimal pain control. Tapentadol is a novel dual-action drug, both stimulating inhibitory μ-opioid receptors (MOR) and mediating noradrenaline reuptake inhibition (NRI) leading to activation of the inhibitory α-2 adrenoceptor. It has been demonstrated to treat effectively both acute and chronic pain. We here demonstrate the efficacy in a model of cancer-induced bone pain.MethodsMRMT-1 mammary carcinoma cells were inoculated into the tibia of 6-week-old rats and 2 weeks after, the neuronal responses to a wide range of peripheral stimulation were evaluated. The recordings were made from wide-dynamic range neurons in lamina V of the dorsal horn before and after administration of tapentadol as well as antagonists of the two mechanisms, naloxone or atipamezole.ResultsWe found marked inhibitions of the neuronal activity with efficacy against mechanical, thermal and electrically evoked activity following tapentadol administration. In addition, the effects of the drug were fully reversible by naloxone and partly by atipamezole, supporting the idea of MOR-NRI dual actions.ConclusionsThese findings add to the mechanistic understanding of cancer-induced bone pain and support the sparse clinical data indicating a possible use of the drug as a therapeutic alternative for cancer patients with metastatic pain complication.

U2 - 10.1002/ejp.530

DO - 10.1002/ejp.530

M3 - Journal article

C2 - 24917026

VL - 19

SP - 152

EP - 158

JO - European Journal of Pain

JF - European Journal of Pain

SN - 1090-3801

IS - 2

ER -