Transient heat hyperalgesia during resolution of ropivacaine sciatic nerve block in the rat

Abstract

Background: Preliminary studies using perineural sciatic ropivacaine in rat demonstrated unexpected heat hyperalgesia after block resolution. To better characterize the time course relative to mechanical anesthesia-analgesia, we tested the hypothesis that ropivacaine 0.5% leads to transient heat hyperalgesia in rats independent of mechanical nociception. We also evaluated functional toxicity (eg, long-term hyperalgesia and/or tactile allodynia 2 weeks after injection).

Methods: Under surgical exposure, left sciatic nerve block was performed in 2 groups of adult male rats-ropivacaine (200 μL, 5 mg/mL; n = 14) versus vehicle (n = 11). The efficacy and duration of block were assessed with serial heat, mechanical (Randall-Selitto testing), and tactile (von Frey-like monofilaments) tests; motor-proprioceptive (rotating rod) and sedation tests were used at 1 and 7 hrs after injection. The presence of nerve injury was assessed by repeating the heat, tactile, and motor tests 12 to 14 days after injection.

Results: Ropivacaine-induced anesthesia was fully manifest at 1 hr after injection. At 3 hrs after injection, heat hypersensitivity was present in the setting of resolved mechanical analgesia. All behavioral measures returned to baseline by 2 weeks after injection. There was no evidence of (i) behavioral sedation, (ii) persistent changes in heat or mechanical sensitivity, or (iii) persistent changes in proprioceptive-motor function at 12 to 14 days after injection.

Conclusions: Ropivacaine 0.5% induces transient heat hyperalgesia in the setting of resolved mechanical analgesia, further suggestive of modality and/or nociceptive fiber specificity. Whether this finding partially translates to "rebound pain" after patients' nerve blocks wear off requires further study.

Figure 1. Heat anesthesia-analgesia followed by shorter latencies to heat after sciatic nerve block with ropivacaine

This is an illustration of nociceptive responses of the treated (left) hindlimb to heat stimuli as a function of treatment and time (P<0.001). The last time point on the X-axis represents behavioral testing before rats were euthanized (postoperative day 12–14). The ropivacaine (RPV) group showed anesthesia at 1 hr after injection (P<0.001), compared to the vehicle group (VEH), followed by a shorter response latency to heat stimuli (†P=0.001) at 3 hr after injection. There was no evidence of transient heat hyperalgesia at 5–7 hr, or long-term heat hyperalgesia at 2 weeks.

Figure 2. Tactile withdrawal threshold (mN) to von Frey monofilament testing after sciatic nerve block with ropivacaine

This is an illustration of nociceptive responses of the treated (left) hindlimb to tactile stimuli as a function of treatment and time. The last time point (\on the X-axis represents behavioral testing before rats were euthanized (postoperative day 12–14). The ropivacaine (RPV) group showed anesthesia at 1 hr after injection (P<0.001), compared to the vehicle group (VEH). There were no statistically significant differences in tactile withdrawal threshold (mN) to von Frey monofilament testing between the RPV and VEH groups at any other time point.

Figure 3. Mechanical anesthesia after sciatic nerve block with ropivacaine as demonstrated with Randall-Selitto testing

This is an illustration of mechanical anesthesia demonstrated with Randall-Selitto testing as a function of treatment and time. The last time point (on the X-axis) represents behavioral testing before rats were euthanized (post operative day 12–14). At baseline, treatments did not significantly differ between RPV (131.9 ± 11.0 g) and VEH (126.9 ± 8.1 g) with respect to withdrawal threshold. At 1 hr after injection, the ropivacaine (RPV) group was anesthetic (249.5 ± 0.5 g) compared with VEH (176.4 ± 21.2 g) as evidenced by a higher withdrawal threshold force (P<0.001). RPV withdrawal thresholds to Randall-Selitto testing returned to baseline and did not significantly differ from VEH by 3 hr after block.