Table 1.

Receptors, ion channels, enzymes with excitatory mode of action, involved in generation and maintenance of NP, potentially targeted by topically administered treatments. Possible site of action of topical agents, addressing given molecular target. Abbreviations: Nav—voltage-gated sodium channels, TRPV1—transient receptor potential vanilloid 1, VGCC—voltage-gated calcium channels, NMDAR—N-methyl-D-aspartate receptors, α1-AR—α1adreno receptors, COX-2—cyclooxygenase-2, NSAID—nonsteroidal anti-inflammatory drug, SNAP-25—synaptosome-associated protein 25.

	Receptor Ion Channel Enzyme	Topical Agent Utilized in Clinical Practice	Possible Site of Action	Reference
EXCITATORY	Nav	Lidocaine Antidepressants: -Amitriptyline -Doxepin Phenytoin Ambroxol TV-45070 Opioids NSAIDs Clonidine	Neurons Keratinocytes	[36,37,38,91,106,114,115,116,117,118,119,120,121,122,123]
	TRPV1	Capsaicin NSAIDs	Neurons Keratinocytes Immune cells	[69,70,76,93,94,97,124,125,126,127,128]
	VGCC	Gabapentin Lidocaine	Neurons Keratinocytes	[39,61,76,91,94,96,129,130,131,132,133]
	NMDAR	Ketamine Antidepressants: -amitriptyline NSAID-Diclofenac	Neurons Keratinocytes Immune cells	[95,134,135,136,137,136,137,138,139,140,141,142]
	α1-AR	Prazosin Antidepressants	Neurons Keratinocytes Immune cells	[31,33,43,44,45,46,67,73,143,144,145]
	COX-2	NSAIDs	Neurons Immune cells Schwann cells	[75,146,147]
	SNAP-25	Botulinum toxin A	Neurons Immune cells Glial cells	[148,149,150,151]