Mechanisms of action of topical drugs for the therapy of NP for excitatory and inhibitory effects
| Mechanism of action of topical agents | Receptor ion channel enzyme | Topical agent utilized in clinical practice | Possible site of action | Reference |
|---|---|---|---|---|
| Mechanism for excitatory effect of drugs | Voltage-gated sodium channels (NaVs) | Lidocaine, amitriptyline, doxepin, phenytoin, ambroxol, TV-45070, opioids, NSAIDs, clonidine | Neurons, keratinocytes | [128–132] |
| TRPV1 | Capsaicin, NSAIDs | Neurons, keratinocytes, immune cells | [133–135] | |
| VGCC | Gabapentin, lidocaine | Neurons, keratinocytes | [136–138] | |
| NMDAR | Ketamine, amitriptyline, diclofenac | Neurons, keratinocytes, immune cells | [139–141] | |
| COX-2 | NSAIDs | Neurons, immune cells, Schwann cells | [142–144] | |
| Mechanism for inhibitory effect of drugs | GABAR | Amitriptyline | Neurons, keratinocytes, immune cells | [145–148] |
| GABAAR | Ketamine, phenytoin | Neurons, keratinocytes, immune cells | [149, 150] | |
| GABABR | Baclofen | Neurons, keratinocytes, immune cells | [151–154] | |
| α2-AR | Clonidine | Neurons | [155–157] | |
| OR | Opioids | Neurons, keratinocytes, immune cells | [158–160] | |
| CR | Cannabinoids | Neurons, keratinocytes, immune cells | [161–163] |
α2-AR: α2 adreno receptors; COX-2: cyclooxygenase-2; CR: cannabinoid receptors; GABAR: γ-aminobutyric acid receptors; GABAAR: γ-aminobutyric acid type A receptors; TV-45070: topical sodium channel inhibitor; NMDAR: NMDA receptors; NSAIDs: Non-steroidal anti-inflammatory drugs; OR: opioid receptors; TRPV1: transient receptor potential vanilloid 1