Morphine and Clonidine Synergize to Ameliorate Low Back Pain in Mice

Table 2

Combination therapy improves therapeutic window.

Strain	Drug(s)	ED50 value (±SE; mg/kg, i.p.)			Therapeutic window
		Motor	Axial	Non-axial	Motor/axial	Motor/non-axial
SPARC-null	Morphine	8 (±6.1)	10 (±4.0)	~35 (±50)	0.8	0.2
	Clonidine	0.3 (±0.3)	0.05 (±0.04)	0.08 (±0.09)	6.8	4.3
	Morphine (+ CLON; 100 : 1)	~56 (±85)	0.08 (±0.23)	3.5 (±6.3)	700	16
WT	Morphine	~17 (±14)	18 (±6.0)	6.0 (±2.0)	0.9	2.8
	Clonidine	0.1 (±0.2)	8.2 (±21)	0.1 (±0.2)	0.01	1.0
	Morphine (+ CLON; 100 : 1)	No efficacy	No efficacy	2.7 (±8.9)	N/A	N/A

The Therapeutic window is the ratio of the ED₅₀ value (mg/kg, i.p.) of the undesired effect (motor impairment) to the desired effect (inhibition of axial or non-axial pain). A larger therapeutic window suggests the drug or drug combination will be analgesic at doses that do not produce motor impairment. ~ indicates that the ED₅₀ value was determined by extrapolation if maximum efficacy was less than 50%. NA = not available (the combination lacked efficacy in the rotarod assay in WT mice). Note the much larger therapeutic window achieved with the addition of clonidine to morphine.