|
Opioid receptor (μ, OPRM1) |
CNS |
Morphine, oxycodone, fentanyl |
OPRM1 agonists inhibit synaptic transmission, activate central inhibitory circuits |
Mixed results; some utility in PHN and DPN. Multiple routes of administration available |
| Voltage-gated sodium channels |
PNS |
Lidocaine, bupivacaine |
Nonselective sodium channel blocker |
Topical application in peripheral NP, e.g., in PHN |
| CNS/PNS |
Carbamazepine, lamotrigine, mexiletine, amitryptiline |
Nonselective sodium channel blockers stabilize an inactive channel state |
Trigeminal neuralgia, phantom limb pain |
|
Calcium channel (N-type, Cav2.2) |
CNS |
ω-conotoxin |
N-type calcium channel blocker reduces neurotransmitter release |
Intrathecal delivery for severe chronic pain |
|
Calcium channel auxiliary subunits (α2δ1 or CACNA2D1) |
CNS/PNS |
Gabapentin, pregabalin |
Bind to the α2δ1-subunit of voltage-gated calcium channels, reduce trafficking of the channels, decrease transmitter release from primary afferents |
Effective in peripheral NP |
| NMDA receptor |
CNS |
Ketamine, memantine, dextromethorphan |
NMDA receptor antagonists reduce central sensitization |
Limited by adverse effects |
|
Monoamine transporters (NAT and SERT) |
CNS |
Tricyclic antidepressants, selective noradrenaline (SNRIs) or serotonin (SSRIs) reuptake inhibitors |
Block monoamine reuptake, reinforce brain stem inhibitory pathways |
Effective in NP, especially PHN and painful diabetic neuropathy |
|
Cannabiniod receptors (CNR1/CNR2) |
PNS, CNS |
δ-9-tetrahydrocannabinol, cannabidiol, synthetic cannabinoids |
CNR1 agonists reduce nociceptor activation and transmitter release. CNR2 suppress immune reactions |
Effective in central pain (multiple sclerosis) |
| TRPV1 |
PNS |
Capsaicin, resiniferatoxin |
TRPV1 agonists desensitize C-fiber nociceptors and provoke their degeneration |
Topical application in peripheral NP |
