Background: Tapentadol [(-)-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol] is a novel analgesic with a dual mode of action: µ opioid receptor (MOR) agonism (K_i = 0.1µM for rat MOR binding) and noradrenaline (NA) reuptake inhibition (K_i = 0.5µM for rat synaptosomal NA reuptake inhibition). Due to its lower depressant effect on the activity of the intestine compared to morphine, as shown in the guinea pig ileum twitch model, tapentadol may be an interesting substance for the treatment of visceral pain.

Methods: The effects of tapentadol and morphine were investigated in three rodent models of visceral pain: mouse phenylquinone writhing, rat colorectal distension, mouse mustard oil-induced colitis.

Results: Tapentadol and morphine showed comparable analgesic effects in all models tested.

	Tapentadol HCl (iv)		Morphine HCl (iv)
Animal Model	ED50 values	MPE* (%) / (dosage)	ED50 values	MPE* (%) / (dosage)
Mouse phenylquinone writhing	0.66 mg/kg	100% (4.64 mg/kg)	0.37 mg/kg	100% (2.15 mg/kg)
Mouse mustard oil-induced colitis
- spontaneous pain	1.47 mg/kg	99% (10 mg/kg)	1.01 mg/kg	110% (4.64 mg/kg)
- referred tactile allodynia	3.75 mg/kg	86% (10 mg/kg)	0.77 mg/kg	103% (4.64 mg/kg)
- referred tactile hyperalgesia	3.93 mg/kg	81% (10 mg/kg)	0.86 mg/kg	102% (4.64 mg/kg)
Rat colorectal distension	5.5 mg/kg	76% (10 mg/kg)	2.3 mg /kg	75% (4.64 mg/kg)

* MPE = maximum possible effect

Conclusions: Tapentadol is a novel centrally acting analgesic with broad efficacy profile in several animal models of visceral pain. Tapentadol shows analgesic efficacy in spontaneous as well as referred parameters of visceral pain.

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