Morphine and Clonidine Synergize to Ameliorate Low Back Pain in Mice

Table 1

Effect of combination therapy on drug potency.

Assay	Strain	Morphine ED50	Clonidine ED50	Observed	Theoretical	Interaction
				combination	combination
				ED50	ED50
Tail suspension (Axial pain)	SPARC-null	10 (±4.0)	0.05 (±0.04)	0.08 (±0.23)	3.3 (±2.1)	Synergistic
	WT	18 (±6.0)	8.2 (±21)	NA	17 (±5.7)	NA
Acetone (cold allodynia)	SPARC-null	~35 (±50)	0.08 (±0.09)	3.5 (±6.3)	6.6 (±6.0)	Additive
	WT	6 (±2.0)	0.1 (±0.2)	2.7 (±8.9)	4.2 (±1.8)	Additive
Rotarod (motor incoordination)	SPARC-null	8 (±6.1)	0.3 (±0.3)	~56 (±85)	6.5 (±4.5)	Additive
	WT	~17 (±14)	0.1(±0.2)	No efficacy	7.3 (±7.4)	NA
Open field (overall activity)	SPARC-null	*0.2 (±0.1)	0.2 (±0.2)	No efficacy	NA	NA
	WT	*0.6 (±0.3)	0.14(± 0.16)	*0.13 (± 0.08)	NA	NA

Morphine and clonidine ED₅₀ values (mg/kg, i.p.) either alone or in combination at a dose ratio of 100 : 1 (observed combination ED₅₀). The Theoretical Combination ED₅₀ is the predicted ED₅₀ for the combination in the absence of any interaction. The interaction indicates if the observed combination ED₅₀ was statistically different from the theoretical combination ED₅₀. ~ indicates that the ED₅₀ value was determined by extrapolation if maximum efficacy was less than 50%. *In the open field assay, morphine had no potency as a sedative but caused hyperactivity. A drug or drug combination was considered to exhibit no efficacy if maximum efficacy was under 30%. NA = not available (it is not possible to calculate these values when one drug lacks efficacy).