Table 2.

Comparison of analgesic properties of N/OFQ and NOP receptor agonists between rodents and NHPs

Administration route	Pain modality	Pharmacological action	Rodents	NHPs
Peripheral	Acute pain	Antinociceptive effects	s.c. N/OFQ in the mouse tail Local antinociception inhibited by naloxone (Kolesnikov and Pasternak, 1999)
		No antinociceptive effects	i.pl. Ro64-6198 in naïve rats (Obara et al., 2005)	s.c. N/OFQ in the NHP tail (Ko et al., 2002)
		Biphasic (low dose: nociceptive vs. high dose: antinociceptive)	i.pl. N/OFQ (0.01 fmol–1 nmol) in the nociceptive flexor test in mice (Inoue et al., 1999)
		No biphasic effects		s.c. N/OFQ (1 pg–30 µg) in the NHP tail withdrawal assay (Ko et al., 2002)
	Capsaicin allodynia	Antiallodynic effects	i.pl. N/OFQ in naïve mice (Sakurada et al., 2005)	s.c. N/OFQ in the NHP tail
				Local antinociception inhibited by J-113397 (Ko et al., 2002)
	Neuropathic pain	Antihypersensitive effects	i.pl. N/OFQ and Ro64-6198 in CCI rats (Obara et al., 2005)
			Local antihypersensitive effect inhibited by Nphe (Obara et al., 2005)
Spinal	Acute pain	Antinociceptive effects	i.t. N/OFQ in the rat and mouse tail flick assay (Xu et al., 1996; King et al., 1997; Tian et al., 1997a)	i.t. N/OFQ in the NHP tail withdrawal assay (Ko et al., 2006; Ko and Naughton, 2009)
			Spinal antinociception inhibited by naltrexone (King et al., 1997) and UFP-101 (Nazzaro et al., 2007) in mice, by naloxone in rats (Jhamandas et al., 1998), by MOP and DOP receptor antagonists in rats (Yu et al., 2002)	Spinal antinociception inhibited by J-113397, not naltrexone (Ko et al., 2006)
		No antinociceptive effects	i.t. Ro64-6198 in naïve rats (Obara et al., 2005)
		Biphasic (low dose: nociceptive vs. high dose: antinociceptive)	i.t. N/OFQ (fmol) in mice (Inoue et al., 1999; Sakurada et al., 1999)
		No biphasic effects		i.t. N/OFQ (1 fmol–1 µmol) in the NHP tail withdrawal assay (Ko and Naughton, 2009)
	Capsaicin allodynia	Antiallodynic effects	i.t. N/OFQ in rats with mechanical allodynia (Nozaki-Taguchi and Yamamoto, 2005)	i.t. UFP-112 in NHPs with thermal allodynia (Hu et al., 2010)
	Neuropathic pain	Antihypersensitive effects	See details in Table 3
Systemic	Acute pain	Antinociceptive effects	i.p. Ro64-6198 in the mouse hot plate test (Reiss et al., 2008)	s.c. Ro64-6198 in the NHP tail withdrawal assay (Ko et al., 2009)
			Systemic antinociception was absent in NOP receptor knockout mice (Reiss et al., 2008)	i.v. Ro64-6198 in the NHP tail withdrawal assay (Ko, 2004; Podlesnik et al., 2011)
				i.m. Ro64-6198 and SCH221510 in the NHP tail withdrawal assay (Cremeans et al., 2012)
				Systemic antinociception inhibited by J-113397 (Ko et al., 2009)
		No antinociceptive effects	i.p. Ro64-6198 in the rat tail flick test (Jenck et al., 2000; Dautzenberg et al., 2001)
			i.p. Ro64-6198 in the mouse tail immersion test (Kotlinska et al., 2003)
		Pronociceptive effects	i.p. Ro64-6198 in the mouse tail flick assay (Reiss et al., 2008)
		Potentiation of MOP receptor agonist-induced antinociception	Ro64-6198 potentiated morphine antinociception in an additive manner (Reiss et al., 2008)	Ro64-6198 potentiated buprenorphine antinociception in a synergistic manner (Cremeans et al., 2012)
	Capsaicin allodynia	Antiallodynic effects		s.c. Ro64-6198 in the NHP thermal allodynia assay (Ko et al., 2009)
	Neuropathic pain	Antihypersensitive effects	i.v. GRT-TA2210 and Ro65-6570 in CCI mice (Linz et al., 2013)
			i.v. and i.p. Ro65-6570 in neuropathic mice and rats (Schiene et al., 2013)
	Inflammatory pain	Antihyperalgesic effects	i.v. GRT-TA2210 in the mouse formalin test (Linz et al., 2013)	s.c. Ro64-6198 in the NHP carrageenan assay (Sukhtankar et al., 2014)
			i.v. Ro65-6570 in the rat formalin and CFA assays (Schiene et al., 2013)

No data are published for fields that are left blank. GRT-TA2210, selective NOP receptor agonist; J-113397, selective NOP receptor antagonist; Nphe, [Nphe1]N/OFQ(1-13)NH2, a selective NOP receptor antagonist; Ro64-6198, Ro65-6570, selective NOP receptor agonists; SCH-221510, selective NOP receptor agonist; UFP-101, selective NOP receptor antagonist; UFP-112, selective NOP receptor agonist.