Table 1.

Animal study characteristics.

First author publication year	Animals				Treatment	Control	Admin. route	Dose	Dosing	Pain model	Outcome measure	Measurement delay since injection*
	Species	Sex	Age (wk)	Weight (g)
Studies on single ketamine administration (n = 21)
Chaplan et al., 19972	Rat (Sprague-Dawley)	Male			Ketamine	Saline	i.t.	100 µg	Single	SNL	Paw withdrawal to a mechanical stimulus	60 min
Christoph et al., 20063	Rats (Sprague-Dawley)	Male		170-310	Ketamine	Saline	i.v.	4.64 mg/kg	Single	CCI	Paw withdrawal to a cold stimulus	15 min, 24 h
Claudino et al., 20184	Rat (Wistar)	Male		200-220	S-ketamine	Vehicle	i.n.	1 mg/kg	Single	CION	Paw withdrawal to a mechanical stimulus	30 min
De Vry et al., 20048	Rat (Wistar)	Male		180-200	Ketamine	Vehicle	i.p.	20 mg/kg	Single	CCI	Paw withdrawal to a mechanical stimulus	30 min
Doncheva et al., 201910	Rat (Wistar)	Male		200-220	Ketamine	Saline	i.p.	50 mg/kg	Single	CCI	Paw withdrawal to a mechanical stimulus	60 min
Fang 201811	Rat (Sprague-Dawley)	Male		180-230	Ketamine	Saline	i.p.	10 mg/kg	Single	SNI	Paw withdrawal to a mechanical stimulus	72 h
Hama and Sagen, 201212	Rat (Sprague-Dawley)	Male		100-150	Ketamine	Vehicle	i.t.	100 µg	Single	SCI	Paw withdrawal to a mechanical stimulus	90 min
Humo et al., 202019	Mouse (C75BL/6)	Male	8		Ketamine	Saline	i.p.	15 mg/kg	Single	CCI	Paw withdrawal to a mechanical stimulus	120 min, 24 h
Kroin et al., 201922	Mouse (D1)	Female		20	Ketamine	Saline	i.p.	10 mg/kg	Single	SNI	Paw withdrawal to a mechanical stimulus	60 min, 72 h
Lim et al., 201325	Mouse (ICR)	Male		25-30	Ketamine	Vehicle	i.t.	100 µg	Single	CCI	Paw withdrawal to a mechanical stimulus	90 min
Mao† et al., 199327	Rat (Sprague-Dawley)	Male		400-500	Ketamine	Saline	i.t.	23.7 µg	Single	CCI	Paw withdrawal to radiant heat	30 min
M'Dahoma 201428	Rat (Sprague-Dawley)	Male	7-8	225-250	Ketamine	Vehicle	i.p.	50 mg/kg	Single	SCI	Paw withdrawal to a mechanical stimulus	30 min
M'Dahoma et al., 201529	Rat (Sprague-Dawley)	Male		175-200	Ketamine	Saline	i.p.	50 mg/kg	Single	CCI	Paw withdrawal to a mechanical stimulus	60 min
Mehta et al., 201230	Rat (Wistar)	Male		180-250	Ketamine	Control	i.p.	25 mg/kg	Single	CCI	Paw licking or jump latency on hot plate	45 min
Mei et al., 201032	Rat (Sprague-Dawley)	Male		180-200	S-ketamine	Saline	i.t.	1000 µg/kg	Single	CCI	Paw withdrawal to a mechanical stimulus	30 min, 72 h
Pan et al., 201840	Rat (Sprague-Dawley)	Male	6-7	200-250	Ketamine	Saline	i.p.	10 mg/kg	Single	SNI	Paw withdrawal to a mechanical stimulus	72 h
Qian et al., 199643	Rat (Sprague-Dawley)	Male		125-150	Ketamine	Saline	i.p.	50 mg/kg	Single	SNL	Paw withdrawal to a mechanical stimulus	15 min
Rodrigues-Filho et al., 200445	Rat (Wistar)	Male		250-300	Ketamine	Saline	i.p.	25 mg/kg	Single	BPA	Paw withdrawal to a mechanical stimulus	30 min
Sasaki et al., 200847	Mouse (C57BL/6J)	Female	6		Ketamine	Vehicle	i.p.	50 mg/kg	Single	PHN	Paw withdrawal to a mechanical stimulus	60 min
Truin et al., 201152	Rat (Sprague-Dawley)	Male		300-350	Ketamine	Saline	i.t.	200 µg	Single	CCI	Paw withdrawal to a mechanical stimulus	45 min
Wang et al., 201153	Rat (Sprague-Dawley)	Male		250-300	Ketamine	Saline	i.p.	10 mg/kg (1 h), 50 mg/kg (24 h)	Single	SNI	Paw withdrawal to a mechanical stimulus	1 h, 24 h
Multiple ketamine administrations or continuous ketamine infusion (n = 11)
Hota et al., 200717	Rat (Wistar)	Male		200-250	Ketamine	Control	Gavage	2.5 mg/kg	1 daily dose for 25 days	SNI	Paw licking latency on hot plate	0 d
Huang et al., 200418	Rat (Sprague-Dawley)	Female		200-250	Ketamine	Saline	i.p.	10 mg/kg	6 days for 4 weeks	SNL	Paw withdrawal to a mechanical stimulus	1 d
Kwon et al., 201423	Rat (Sprague-Dawley)	Male		180-200	Ketamine	Saline	s.c.	40 mg/kg per day	7-day infusion	SNL	Paw withdrawal to a mechanical stimulus	0 d
Mak et al., 201526	Rat (Wistar)	Male			Ketamine	Control	s.c.	20 mg/kg per day	5-day infusion	STZ DN	Paw withdrawal to a mechanical stimulus	14 d
Mao† et al., 199327	Rat (Sprague-Dawley)	Male		400-500	Ketamine	Saline	i.t.	23.7 µg	4 daily doses for 3 days	SNL	Paw withdrawal to radiant heat	7 days after last dose
Mei‡ 2009a,c31 Mei 2009b,d	Rat (Sprague-Dawley)	Male		180-200	S-ketamine	Saline	i.t. i.p.	100 µg/kg 20 mg/kg	1 dose/day for 3 or 7 days	SNL	Paw withdrawal to a mechanical stimulus	0 d
Mei et al., 2011a33	Rat (Sprague-Dawley)	Male		180-200	S-ketamine	Saline	i.t.	300 µg/kg	1 dose/day for 3 days	SNL	Paw withdrawal to a mechanical stimulus	0 d
Mei et al., 2011b34	Rat (Sprague-Dawley)	Male		180-200	S-ketamine	Saline	i.t.	300 µg/kg	1 dose/day for 3 days	SNL	Paw withdrawal to a mechanical stimulus	0 d
Salvat§ et al., 2018a46 Salvat 2018b	Mouse (6J)	Male	6		Ketamine	Saline	i.p.	15 mg/kg	2 doses/day for 10 days (0-10 after CCI); 2 doses/day (25-35 days after CCI)	CCI	Paw withdrawal to a mechanical stimulus	15 d and 34 d
Swartjes 201150	Rat (Sprague-Dawley)	Female	9	230	Ketamine	Saline	i.v.	9 mg/kg per day	5-day infusion	SNI	Paw withdrawal to a mechanical stimulus	28 d
Swartjes 201351	Mouse (C57BL/6)	Female			Ketamine	Vehicle	i.p.	50 mg/kg	In week 1, every other day 1 dose, followed by weekly dosing in week 2-6	SNI	Paw withdrawal to a mechanical stimulus	0 d

Ketamine is the racemic mixture, S-ketamine is the S-enantiomer of ketamine.

^*Time points included in the meta-analysis.

^†Mao et al.²⁷ performed 2 independent comparisons: one comparing a single ketamine administration vs saline and one comparing single multiple administrations vs multiple saline administrations.

^‡Mei et al.³³ performed 4 independent comparisons: S-ketamine vs saline administered through the intrathecal route and S-ketamine vs saline administered intraperitoneally with 1 dose per day for 3 and for 7 days.

^§Salvat et al.⁴⁶ performed 2 independent comparisons: one comparing ketamine administration on days 0 to 10 after surgery for CCI and one comparing ketamine administered on days 25 to 35 after surgery for CCI.

Neuropathic pain models: BPA, brachial plexus avulsion; CCI, chronic constriction injury; CION, constriction of infraorbital nerve; PHN, postherpetic neuralgia; Route of administration: i.p., intraperitoneal; i.t, intrathecal; i.v, intravenous; i.n, intranasal; s.c, subcutaneous; SNI, spared nerve injury; SNL, spinal nerve ligation; STZ DN, streptozotocin-induced diabetic neuropathy.