Table 6.
Targets for prevention of secondary hyperalgesia induction in humans.
| Target | Substance | Action at target | Volunteer model effect | Volunteer model used | Clinical effect | Clinical context | References volunteers | References clinical |
|---|---|---|---|---|---|---|---|---|
| Stimulus-induced hyperalgesia | ||||||||
| Opioid receptors | alfentanil | agonist | X | capsaicin | n/a | n/a | [218,219] | |
| fentanyl | agonist | n/a | n/a | X | tested 5 days after back surgery | -- | [169,193] | |
| remifentanil | agonist | X | heat/capsaicin | n/a | n/a | [222] | ||
| morphine | agonist | X | capsaicin heat/capsaicin burn | X | tested 24 h after hysterectomy | [220,221,224] | [233] | |
| hydromorphone | agonist | X | heat/capsaicin | n/a | n/a | [223] | ||
| Locoregional anaesthesia | epidural anaesthesia | multiple | n/a | n/a | X | tested 3 days after colon surgery | -- | [161] |
| lidocaine | Na+-channel antagonist | X | skin incision capsaicin | n/a | n/a | [168,178] | ||
| Na+ channels, systemic | lamotrigine | antagonist | 0 | capsaicin | n/a | n/a | [225] | |
| 4030W92 | antagonist | 0 | capsaicin | n/a | n/a | [225] | ||
| NK1R Descending inhibition | aprepitant | antagonist | 0 | transdermal electric | n/a | n/a | [227] | |
| desipramine | noradrenaline/5-HT reuptake inhibitor | 0 | capsaicin | n/a | n/a | [226] | ||
| NMDAR | ketamine | antagonist | X | HFS/LTP capsaicin burn | X | tested 7 days after renal surgery, 3 days after colon surgery | [20,224,252] | [160,191] |
| VGCC | pregabalin | modulation at α2δ-subunit | X | transdermal electric | n/a | n/a | [227] | |
| gabapentin | modulation at α2δ-subunit | X/0 | transdermal electric, capsaicin | n/a | n/a | [228-230] | ||
| Opioid-induced hyperalgesia | ||||||||
| General anaesthesia | propofol | 0 | transdermal electric/RW | n/a | n/a | [232] | ||
| α2-adrenergic receptors | clonidine | agonist | 0 | transdermal electric/RW | n/a | n/a | [189] | |
| COX-2 | parecoxib | antagonist | 0 | transdermal electric/RW | n/a | n/a | [231] | |
| NMDAR | ketamine | antagonist | X | transdermal electric/RW | X | tested 48 hours after major abdominal surgery with high-dose remifentanil infusion | [189] | [212] |
X, complete block or significant inhibition of secondary hyperalgesia induction
0, no effect on secondary hyperalgesia induction
RW = remifentanil withdrawal
n/a = not available