Table 3.

Preclinical Analgesic Effect of Acetaminophen by PO, IT, IP/SC, IV, IT, ICV Administration in Neuropathic Models

	Study	Test Model	Nociceptive State	Vehicle	Specie Sex (M/F)	Effect of APAP	PO mg/kg	IP/SC/IPLT mg/kg	IV mg/kg	IT µg	ICV µg	Reference
1.	Antinociception effect of acetaminophen in model of diabetic chronic constriction injury pain	Weight bearing Tail flick	Chronic constriction injury	Saline	Rat/M	Decreased Behavior Dose dependent		100–400				Munro et al 2016138
2.	Acetaminophen interact with morphine and tramadol analgesia for the treatment of neuropathic pain	Von Frey	Tibial neuroma transposition model	Saline	Rat/M	No change	20–1000					Shinozaki et al 2015104
3.	Antinociception effect of acetaminophen in model of diabetic neuropathy	Von Frey Tail flick	Streptozotocin induced diabetic model	Saline	Mice/M	Increased threshold Dose dependent	5–100					Micov et al 2015103
4.	Antihyperalgesia by codelivery of N-palmitoylethanolamide and APAP	Formalin test	Streptozotocin induced diabetic model	Saline	Rat/M	Decreased Behavior Dose dependent		3–300 μg (IPLT)				Déciga-Campos and Ortiz-Andrade 2015156
5.	Antinociceptive effect of APAP in neuropathic pain	Hot plate Von Frey Cold allodynia	Chung ligation	Saline	Rat/M	Increased threshold Dose dependent		25–300				Im et al 2012122
6.	Cannabinoid receptor-mediated antinociception with neuropathic spinal cord injury pain	Von Frey	Neuropathic spinal cord injury pain	Saline	Rat/M	Increased threshold		100				Hama and Sagen 2010137
7.	NCX-701 (nitro-APAP) and co-administration with gabapentin	Von Frey Electrical stimuli	Seltzer model	Saline	Rat/M	No change				15–960 μmol/kg		Curros-Criado and Herrero 2009148
8.	COX3 inhibitors not attenuate streptozotocin-induced mechanical hyperalgesia	Von Frey	Streptozotocin induced diabetic model	Saline	Rat/M	No change				1, 7 mg		Matsunaga et al 2007147
9.	Local antinociceptive effects of APAP and cannabinoid receptors	Von Frey Hot plate	Neuropathic pain (Seltzer)	Saline	Mice/M	Increased threshold		100 ng (IPLT)				Dani et al 2007155
10.	Allodynia and hyperalgesia suppression by a novel analgesic in experimental neuropathic pain	Von Frey Hot plate	Neuropathic pain (Bennett)	45% 2-cyclodex in saline	Rat/M	Increased threshold				300		Cui et al 2006142
11.	Attenuation of mechanical allodynia chemotherapy-induced neuropathic pain	Von Frey	Vincristine-induced neuropathic pain animal model	20% DMSO	Rat/M	Increased threshold	151–2265					Lynch et al 200480