Table 7.

Targets for modulation of established secondary hyperalgesia in humans.

Target	Substance	Action at target	Volunteer model effect	Volunteer model used	Clinical effect (neurop athic pain)	Comment re. hyperalgesia	References volunteers	References clinical
Stimulus-induced hyperalgesia
Opioid receptors	alfentanil	agonist	X	transdermal electric	X	only ongoing and evoked pain	[176]	[263]
	alfentanil	agonist	X/0	capsaicin	n/a	n/a	[250-252]	n/a
	remifentanil	agonist	X	transdermal electric	n/a	n/a	[189]	n/a
	morphine	agonist	0	burn	n/a	n/a	[253]	n/a
	buprenorphine	Partial agonist- antagonist	XX	transdermal electric	n/a	n/a	[254]	n/a
COX	paracetamol, parecoxib	COX/COX2 inhibition	XX	transdermal electric	n/a	n/a	[259]	n/a
	ibuprofen	COX inhibition	0	burn	n/a	n/a	[260]	n/a
Na+ channels, systemic	lidocaine	antagonist	XX	transdermal electric	n/a	n/a	[176]	n/a
	lidocaine	antagonist	X	capsaicin	X	only evoked pain	[256]	[263]
	lamotrigine	antagonist	0	heat/capsaicin	n/a	n/a	[223]	n/a
General anaesthesia	propofol		X	transdermal electric	n/a		[262]	n/a
Adenosine receptors	adenosine	agonist	X	transdermal electric	n/a	n/a	[261]	n/a
Descending inhibition	venlafaxine	noradrenaline/5-HT reuptake inhibitor	n/a	n/a	X	evoked pain + area	n/a	[267]
NMDAR	ketamine	antagonist	X	burn	X	ongoing and evoked pain + area	[250,253,255,256]	[263,265]
	ketamine	antagonist	X/0	capsaicin	n/a	n/a	[250-252,256]	n/a
	S-ketamine	antagonist	XX	transdermal electric	n/a	n/a	[176]	n/a
	dextro-methorphan	antagonist	X	burn	n/a	n/a	[257]	n/a
VGCC	gabapentin	modulation at α2δ-subunit	X	heat/capsaicin	X	n/a	[258]	n./a

X, complete block or significant inhibition of established secondary hyperalgesia during drug effect

XX, complete block or significant inhibition of established secondary hyperalgesia outlasting drug effect

0, no effect on established secondary hyperalgesia

n/a = not available