Analgesic effects of the selective blocking of descending facilitation targeting μ, opioid receptor positive neurons in a rat model of bone cancer pain

Objective To investigate analgesic effects of the selective blocking of descending facilitation targeting μ opioid receptor positive neurons in the rostral ventromedial medulla ( RVM) in a rat model of bone cancer pain. Methods Forty-eight adult female Wistar rats weighing 180-200 g were randomly divided into 6 groups: group Ⅰ control ( n = 3) ;group Ⅱ bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells ( n = 9) ;group Ⅲ-Ⅵ received a single intra-RVM micro-injection of PBS (group Ⅲ), dermorphin (group Ⅳ) , saporin (group Ⅴ) and dermorphin-saporin ( group Ⅵ) respectively at 28 days before intra-tibia inoculation ( n = 9 each) . Starting from 3 to 20 days after intra-tibia inoculation, mechanical allodynia was assessed and recorded. The animals were sacrificed on 7, 14 and 20 days after intra-tibia inoculation, after repetitive non-noxious tactile stimulation of the hindpaw. The total number of Fos-positive neurons in the spinal dorsal horn was measured as a marker indicative of central sensitization. Results The animals developed nociceptive hypersensitivity after intra-tibia cancer cell inoculation in group Ⅱ -Ⅵ . Nociceptive hypersensitivity was significantly decreased during 4-7 days after the onset of nociception in group Ⅵ (dermorphin-saporin). The number of Fos positive neurons in bilateral spinal dorsal horn was significantly increased by intra-tibia inoculation of cancer cells in group Ⅱ-Ⅵ as compared with control group and was significantly lower at day 14 and 20 after inoculation in group Ⅵ (dermorphin-saporin) than in group Ⅱ - Ⅴ.Conclusion Selective blocking of descending facilitation targeting μ opioid receptor positive neurons in RVM can effectively reduce nociceptive hypersensitivity induced by intra-tibia inoculation of Walker56 mammary gland carcinoma cells. Key words: Receptors; opioid; Pain; Analgesia