Table 7

Parameters and results of published studies investigating the effect on nociceptive sensitivity of spinally (i.t.)-injected OFQ/N

Effect	Species	Strain^7-a	Sex	Assay^7-b	Control^7-c	Intensity^7-d	Dose^7-e	Reference
							nmol, i.t.
Spontaneous nociception
	Mouse	ddY	♂	SBL	Veh	N.A.	3 × 10⁻⁹–3 × 10⁻⁵ ^7-f	Inoue et al., 1999; Sakurada et al., 1999b, 2000
Hyperalgesia/allodynia
	Mouse	ddY	♂	Probe	Veh	N.A.	5.5 × 10⁻⁴–0.28^7-f	Okuda-Ashitaka et al., 1996; Hara et al., 1997; Minami et al., 2000
	Rat	SD	♀	FR	None	N.A.	<0.055	Xu et al., 1996, 1999b
	Mouse	ddY	♂	HP	Veh ⁺ BL	14 s	≥2.75 × 10⁻⁹/kg	Hara et al., 1997, 2000;Minami et al., 1997
	Mouse	ddY	♂	FR	None	N.A.	1 × 10⁻⁷–1^{^7-f}	Inoue et al., 1999
	Mouse	ddY	♂	HT	Veh	9 s	≥1.5 × 10⁻⁶
				TWrh	Veh ⁺BL	8 s	≥1.5 × 10⁻⁶	Sakurada et al., 1999a,c
Analgesia
	Rat	SD	♂	FR	None	N.A.	≥0.55
				TWrh	BL	N.R.	≥0.55	Xu et al., 1996
	Mouse	CD-1	♂	TWrh	BL	2.5 s	≥2.75	King et al., 1997
	Rat	SD	♂	TWrh	BL	4 s	5.5	Hao et al., 1997
	Rat	Wistar	♂ ⁺♀	TWrh	Veh ⁺ BL	5 s	≥3	Tian et al., 1997a,b
	Rat	SD	♂	F	Veh	5%, 50 μl	≥3.3	Erb et al., 1997
	Rat	SD	♂	F	Veh	5%, 50 μl	≥1.7	Yamamoto et al., 1997a, 2000b; Yamamoto and Sakashita, 1999a
	Rat	SD	♂ ⁺ ♀	TWrh	Veh	4 s	≥0.17	Hao et al., 1998 ^7-g
	Rat	SD	♂	F	Veh	5%, 50 μl	≥5	Hao and Ogawa, 1998
	Mouse	ICR	♂	F	Veh	0.5%, 25 μl	≥1	Kamei et al., 1999b ^7-h
	Mouse	ICR	♂	TWrh	BL	6 s	≥1	Kamei et al., 1999a ^7-i
	Rat	SD	N.R.	TWhw	Veh ⁺ BL	6 s	0.55	Wang et al., 1999c ^7-j
	Rat	SD	♂	F	Veh	5%, 150 μl	≥0.055	Wang et al., 1999a
	Mouse	ddY	♂	F	Veh ⁺ NI	2%, 20 μl	≥0.17	Nakano et al., 2000 ^7-k
No hyperalgesia or analgesia
	Mouse	NMRI	♂	TWrh	Veh	7 s	10	Reinscheid et al., 1995
	Mouse	SW	♂ ⁺♀	TWhw	Veh ⁺ BL	3.5 s	10	Grisel et al., 1996 ^7-l
	Rat	SD	♂	HP	Veh ⁺ BL	20 s	17	Yamamoto et al., 1997a
	Rat	SD	♂	HT	Veh ⁺ BL	11 s	17	Yamamoto and Nozaki-Taguchi, 1997; Yamamoto et al., 2000a
	Rat	SD	♂	VF	Veh	60 g	17	Yamamoto and Sakashita, 1999b
	Mouse	ICR	♂	TWhw	Veh ⁺BL	N.R.	0.055–3
	Rat	SD	♂	TWhw	Veh ⁺BL	N.R.	10
	Rat	SD	♂	HP	Veh ⁺BL	N.R.	10
	Rat	SD	♂	VF	None	N.R.	10	Vanderah et al., 1998
Anti-analgesia
	Rat	SD	♂	PP	Veh ⁺BL	N.R.	0.5–5
				TWrh	Veh ⁺ BL	2 s	0.5–5	Jhamandas et al., 1998 ^7-m
	Rat	SD	♀	FS	Veh ⁺BL	N.R.	≥1	Dawson-Basoa and Gintzler, 1997 ^7-n
	Mouse	CD-1	♂	TWrh	Veh ⁺ BL	3 s	0.0055	Rady et al., 2001 ^7-o
Hyperalgesia and anti-analgesia
	Rat	SD	♂	TWrh	???	???	≥0.055^7-p	Zhu et al., 1998 ^7-q
	Rat	SD	♂	TWrh	???	???	≥0.055^7-p	Zhang et al., 1997 ^7-r
Anti-hyperalgesia/allodynia
	Rat	SD	♂	HT	Veh ⁺BL	11 s	17	Yamamoto et al., 1997b,2000a ^7-s
	Rat	SD	♂	VF	Veh	50 g	17	Yamamoto and Sakashita, 1999b ^7-t
	Rat	SD	♂ ⁺ ♀	TWrh	Veh	4 s	≥0.55
				VF	Veh	80 g	≥1.7	Hao et al., 1998 ^7-u

N.A., not applicable; N.R., not reported; ???, unknown.
↵7-a Strain abbreviations: CD-1, Hsd:ICR; ddY, an inbred strain; ICR, Institute for Cancer Research (Swiss-derived); NMRI, a Swiss-derived European strain; SD, Sprague-Dawley; SW, Swiss-Webster.
↵7-b Assay abbreviations: HP, hot-plate test; HT, Hargreaves' test of paw-withdrawal from radiant heat; F, formalin test; FR, spinal flexor reflex; FS, electric footshock test; Probe, behavioral response to stroking on the flank with a paintbrush; PP, paw pressure (Randall-Selitto) test; SBL, caudally-directed scratching, biting, and licking behavior; TWrh, radiant heat tail-withdrawal (tail-flick) test; TWhw, hot water tail-withdrawal test; VF, Von Frey test of mechanical sensitivity.
↵7-c Control group abbreviations: All, all of the following were used; BL, comparison with baseline latencies; Veh, comparison with vehicle group; NI, comparison with non-injected group.
↵7-d For thermal assays, baseline latency or latency of control group is provided. For other assays, actual intensity parameters are listed.
↵7-e Effective OFQ/N dose or dose range. Many of these studies investigated a wider overall dose range than that shown.
↵7-f Biphasic dose-response relationship observed.
↵7-g Analgesic effect was obtained in contralateral paws of spinally-injured, nerve-irradiated and inflamed animals.
↵7-h In contrast to all other investigations in this section employing the formalin test, these investigators only observed an analgesic effect in the acute/early phase (0–5 min) of the biphasic formalin test.
↵7-i In mice made diabetic with injections of streptozotocin, OFQ/N was even more potent, producing significant analgesia at a dose of 0.1 nmol.
↵7-j In addition to a mild analgesic effect, i.t. OFQ/N produced an impressive potentiation of endomorphin-1 analgesia.
↵7-k Hyperalgesic effects on tonic phase formalin licking were seen at a dose of 10 pg.
↵7-l This study obtained an almost significant (p = 0.053) potentiation of spinal morphine analgesia by OFQ/N.
↵7-m Anti-analgesic effect against systemic morphine analgesia. A dose of 10 nmol failed to block morphine analgesia and actually prolonged its duration. These investigators also demonstrated OFQ/N analgesia in the TWrh and PP tests, but only at much higher doses (50 and 100 nmol).
↵7-n Anti-analgesic effect against gestational and steroid-induced analgesia. In non-pregnant animals, no effect of OFQ/N on nociception was seen.
↵7-o Anti-analgesic effect against spinal morphine analgesia.
↵7-p Dose at which anti-analgesic effects were noted. Hyperalgesia was only seen at higher doses.
↵7-q Anti-analgesic effect against fentanyl and U50,488 analgesia.
↵7-r Anti-analgesic effect against electroacupuncture analgesia.
↵7-s Blocked thermal hyperalgesia after a Bennett and Xie (1988) model neuropathic injury in one study, and after a Seltzer et al. (1990) model neuropathic injury in the other. In a subsequent study, the finding in the Bennett model was weakly replicated, but the finding in the Seltzer model appeared not to be replicated.
↵7-t A partial, and naloxone-sensitive blockade of mechanical allodynia from skin incision.
↵7-u Blocked thermal hyperalgesia, mechanical allodynia, and cold allodynia after carrageenan inflammation, peripheral nerve injury, or ischemic spinal cord injury.