Table 2.
Novel target strategies that may increase the opioid analgesic efficacy in neuropathic pain.
| Chemokine/ Chemokine Receptors Axis |
Target | Chemokine/ Chemokine Receptor Inhibitors |
Effects on Opioid Efficacy under Neuropathic Pain |
|---|---|---|---|
| CCL1/CCR8 | CCL1 | Neutralizing antibody |
↑ Analgesic effects of morphine and buprenorphine (STZ, mice) [251] |
| CCL2/CCR2- CCR4 | CCL2 | Neutralizing antibody |
↑ Analgesic effects of morphine and buprenorphine (CCI, mice) [252] |
| CCR2 | RS504393 (antagonist) |
↑ Analgesic effects of morphine and buprenorphine (CCI, rats) [253] | |
| Cenicriviroc (antagonist) |
↑ Analgesic effects of morphine and buprenorphine (CCI, rats) [248] | ||
| CCR4 | C021 (antagonist) |
↑ Analgesic effects of morphine and buprenorphine (CCI, mice) and delays the development of morphine-induced tolerance [255] | |
| CCL3- CCL4- CCL5/CCR5 | CCR5 | Maraviroc (antagonist) |
↑ Analgesic effects of morphine and buprenorphine (CCI, rats) [249] |
| Cenicriviroc (antagonist) |
↑ Analgesic effects of morphine and buprenorphine (CCI, rats) [248] | ||
| CCL3- CCL9/CCR1 | CCL3 | Neutralizing antibody |
↑ Analgesic effects of morphine (STZ, mice) [256] |
| CCL9 | Neutralizing antibody |
↑ Analgesic effects of morphine (STZ, mice) [256] | |
| CCR1 | J113863 (antagonist) |
↑ Analgesic effects of morphine and buprenorphine (STZ, mice; CCI, rats) [250,256] | |
| CCL7/CCR2 | CCL7 | Neutralizing antibody |
↑ Analgesic effects of morphine and buprenorphine (CCI, mice) [252] |
| CCL7- CCL11/CCR3 | CCR3 | SB328437 (antagonist) |
↑ Analgesic effects of morphine and buprenorphine (CCI, rats) [257] |
| CXCL4- CXCL9- CXCL10- CXCL11- CCL21/ CXCR3 |
CXCL10 | Neutralizing antibody |
↑ Analgesic effects of morphine (BCP, rats) [262] |
| CXCL11 | Neutralizing antibody |
↑ Analgesic effects of morphine (BCP, rats) and attenuates morphine-induced tolerance [259] | |
| CXCR3 | NBI-74330 (antagonist) |
↓ Levels of CXCL4, CXCL9, CXCL10, CXCL11 and CCL21 in DRG and spinal cord (CCI, rats) ↑ Analgesic effects of morphine but not of buprenorphine [260] |
|
| CXCL13/ CXCR5 |
CXCR13 | Neutralizing antibody |
↑ Analgesic effects of morphine (BCP, rats) and prevents the development of morphine-induced tolerance [261] |
| CXCR5 | siRNA | ↑ Analgesic effects of morphine (BCP, rats) [258] |
Abbreviations: BPC-bone cancer pain; CCI-chronic constriction injury; STZ-streptozotocin diabetic neuropathy; siRNA-small interfering RNA.