Analgesia Targeting IB4-Positive Neurons in Cancer-Induced Mechanical Hypersensitivity

作者：Ye Yi; Dang Dongmin; Viet Chi T; Dolan John C; Schmidt Brian L^*

来源：Journal of Pain, 2012, 13(6): 524-531.

DOI：10.1016/j.jpain.2012.01.006

• delta-opioid receptor (DOR)
• mu-opioid receptor (MOR)
• NGF
• isolectin 84
• cancer pain

Cancer patients often suffer from pain and most will be prescribed mu-opioids. mu-opioids are not satisfactory in treating cancer pain and are associated with multiple debilitating side effects. Recent studies show that mu and delta opioid receptors are separately expressed on IB4 (-) and IB4 (+) neurons, which control thermal and mechanical pain, respectively. In this study we investigated 1134 (+) and IB4 (-) neurons in mechanical and thermal hypersensitivity in an orthotopic mouse oral cancer model. We used a delta opioid receptor agonist and a P2X(3) antagonist to target IB4 (+) neurons and to demonstrate that this subset plays a key role in cancer-induced mechanical allodynia, but not in thermal hyperalgesia. Moreover, selective removal of IB4 (+) neurons using IB4-saporin impacts cancer-induced mechanical but not thermal hypersensitivity. Our results demonstrate that peripherally administered pharmacological agents targeting IB4 (+) neurons, such as a selective delta-opioid receptor agonist or P2X(3) antagonist, might be useful in treating oral cancer pain.
Perspective: To clarify the mechanisms of oral cancer pain, we examined the differential role of IB4 (+) and 1134 (-) neurons. Characterization of these 2 subsets of putative nociceptors is important for further development of effective clinical cancer pain relief.

• 出版日期2012-6