Effect of delayed intrathecal administration of capsaicin on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats

Figures & data

Table 1 Summary of experimental protocol

	Capsaicin/vehicle given 2 weeks after CCI	Capsaicin given 3 days after CCI
Group 1 (n=9)	150 μg/100 μL of cap in 5 minutes
Group 2 (n=8)	300 μg/200 μL of cap in 24 hours at 8 μL/hour
Group 3 (n=9)		300 μg/200 μL of cap in 24 hours at 8 μL/hour
Group 4 (n=6)	200 μL of vehicle in 24 hours at 8 μL/hour
Group 5 (n=9)	150 μg/100 μL of cap in 72 hours at 1 μL/hour
Group 6 (n=8)	100 μL of vehicle in 72 hours at 1 μL/hour

Abbreviations: cap, capsaicin; CCI, chronic constriction injury.

Figure 1 Intrathecal capsaicin increased PWL to noxious thermal stimulation in paw ipsilateral to nerve injury.

Notes: PWL of the hind paw to noxious thermal stimulation at three time points: 1) preinjury baseline; 2) CCI (average of two or three measurements); and 3) the treatment (average of three measurements). *Indicates significant difference (P<0.05) between CCI and treatment; ^‡indicates significant difference (P<0.05) between treatment and preinjury baseline; ^†indicates significant difference (P<0.05) between CCI and preinjury baseline. CCI significantly shortened the PWL in all six groups. Two weeks after CCI, fast infusion of capsaicin significantly elevated PWL and abolished thermal hyperalgesia (group 1); chronic infusions of capsaicin at 8 μL/hour (group 2) significantly elevated PWL and restored it to preinjury baseline; chronic infusion of capsaicin at 1 μL/hour (group 5) significantly elevated PWL but failed to restore it to preinjury baseline; infusions of vehicle at 8 μL/hour (group 4) and 1 μL/hour (group 6) did not significantly affect PWL. Capsaicin administered at the third day after the CCI did not significantly affect PWL (group 3).
Abbreviations: cap, capsaicin; veh, vehicle; PWL, paw withdrawal latency; CCI, chronic constriction injury.

Figure 2 Intrathecal capsaicin increased PWL to noxious thermal stimulation in paw contralateral to nerve injury.

Notes: PWLs at three time points were presented as: preinjury baseline; CCI (average of two or three measurements); and treatment (average of three measurements). *Indicates significant difference (P<0.05) between CCI and treatment; ^‡indicates significant difference (P<0.05) between treatment and preinjury baseline. Unilateral CCI of sciatic nerve did not alter PWL of contralateral hind paw from preinjury baseline. Two weeks after CCI, fast infusion of capsaicin (group 1) significantly elevated PWL from CCI and preinjury baseline. Chronic infusion of capsaicin at 8 μL/hour (group 2) significantly elevated PWL from CCI.
Abbreviations: cap, capsaicin; veh, vehicle; PWL, paw withdrawal latency; CCI, chronic constriction injury.

Figure 3 Intrathecal capsaicin produced a more profound increase in the thermal response threshold in the injured side as compared to the uninjured side.

Notes: Capsaicin elicited an increase in the thermal response threshold on both the uninjured side (open bar) and the injured side (solid bar) in group 1 and group 2. Fast infusion (group 1) and chronic infusion of capsaicin at 8 μL/hour (group 2) elicited a more profound elevation in PWL on the injured side as compared to the uninjured side. *Represents significant difference at P≤0.05 comparing two paws.
Abbreviations: cap, capsaicin; veh, vehicle; PWL, paw withdrawal latency; CCI, chronic constriction injury.

Table 2 Pairwise comparisons of averaged PWLs to thermal stimulation in the paw ipsilateral to CCI at three different time points – preinjury baseline, CCI, and treatment

	Preinjury baseline versus CCI(s)	Preinjury baseline versus treatment(s)	CCI versus treatment(s)
Group 1 (n=9)	14.28 versus 8.40 (P<0.0001)†	14.28 versus 15.81 (P<0.004)‡	8.4 versus 15.81 (P<0.0001)*
Group 2 (n=8)	15.75 versus 9.78 (P<0.0001)†	15.75 versus 13.40 (P=0.1771)	9.78 versus 13.40 (P<0.0001)*
Group 3 (n=9)	13.58 versus 8.19 (P<0.0001)†	13.58 versus 8.84 (P<0.0001)‡	8.19 versus 8.84 (P=0.4247)
Group 4 (n=6)	12.58 versus 8.15 (P<0.0001)†	12.58 versus 8.14 (P<0.0001)‡	8.14 versus 8.81 (P=0.4922)
Group 5 (n=9)	14.30 versus 8.49 (P<0.0001)†	14.30 versus 11.17 (P<0.0001)‡	8.49 versus 11.17 (P=0.0014)*
Group 6 (n=8)	14.50 versus 9.19 (P<0.0001)†	14.50 versus 10.17 (P<0.0001)‡	9.19 versus 10.17 (P=0.2470)

Notes:

† Indicates significant difference (P<0.05) comparing CCI and preinjury baseline

‡ indicates significant difference (P<0.05) comparing treatment and preinjury baseline

* indicates significant difference (P<0.05) comparing CCI and treatment.

Abbreviations: PWL, paw withdrawal latency; CCI, chronic constriction injury.

Figure 4 Intrathecal capsaicin did not alter PWT to mechanical stimulation in the injured side.

Notes: PWT of the hind paw ipsilateral to the injury to mechanical stimulation. PWTs at three time points were presented as: preinjury baseline, CCI (the average of two measurements), and treatment (the average of three measurements). ^‡Indicates significant difference (P<0.05) between treatment and preinjury baseline; ^†represents significant difference at P≤0.05 when comparing CCI with preinjury baseline. CCI significantly decreased PWT from preinjury baseline in all five groups (group 3 is not presented). Neither capsaicin nor vehicle administration restored PWT to preinjury baseline.
Abbreviations: PWT, paw withdrawal threshold; cap, capsaicin; veh, vehicle; CCI, chronic constriction injury.