Activation of spinal alpha-7 nicotinic acetylcholine receptor attenuates remifentanil-induced postoperative hyperalgesia.
The activation of alpha-7 nicotinic acetylcholine receptors (α7-nAchRs) are currently being considered as novel therapeutic approaches for managing hyperalgesia in inflammation and chronic neuropathic pain, but the role of a7-nAChRs on opioids induced hyperalgesia remain unknown. The present study investigated the effects of α7-nAChRs selective agonists PHA-543613 and type II positive allosteric modulators (PAMs) PNU-120596 in remifentanil induced postoperative hyperalgesia. As the results shown, intrathecal treatment with both α7-nAChRs agonists and type II PAMs could attenuate remifentanil induced hyperalgesia by increasing paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). Furthermore, we also investigated the protein level of proinflammatory cytokines and phosphorylation N-methyl-d-aspartate receptor 2B subunit (p-NR2B) in the spinal cord. Our data indicated that activation of α7-nAchRs decreased the proinflammatory cytokines (TNF-α, IL-6) and p-NR2B protein level in the spinal cord. The depression of the increased levels of proinflammatory cytokines and p-NR2B after remifentanil treatment may contribute to the anti-hyperalgesia effects of PHA-543613and PNU-120596 via α7-nAChRs. Therefore, our findings demonstrated that α7-nAChRs may be potential candidates for treating opioids induced hyperalgesia.
Department of Anesthesiology, Drum Tower Hospital of Clinic Department of Nanjing Medical University Nanjing 210008, Jiangsu, People's Republic of China.
Wei
W
Zhang
Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University Nanjing 210008, Jiangsu Province, China.
Yue
Y
Liu
Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University Nanjing 210008, Jiangsu Province, China.
Bailing
B
Hou
Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University Nanjing 210008, Jiangsu Province, China.
Xiaoping
X
Gu
Department of Anesthesiology, Drum Tower Hospital of Clinic Department of Nanjing Medical University Nanjing 210008, Jiangsu, People's Republic of China.
Zhengliang
Z
Ma
Nicotinic receptors; hyperalgesia; remifentanil