Peritoneal administration of Met-RANTES attenuates inflammatory and nociceptive responses in a murine neuropathic pain model.

UNLABELLED: The C-C motif chemokine ligand 5 (CCL5; also known as regulated on activation, normal T expressed and secreted, or RANTES) is a member of the CC family of chemokines that specifically attract and activate leukocytes to sites of inflammation. Although CCL5 has been implicated in the processing of pain, its detailed mechanisms of action are still unknown. In this study, we investigated the potential of the Met-RANTES, a selective CCL5 receptor antagonist, via peritoneal administration to modulate the recruitment of inflammatory cells in injured sites and attenuate nociceptive responses in a neuropathic pain model in mice. Nociceptive sensitization, immune cell infiltration, multiple cytokine secretion, and opioid peptide expression in damaged nerves were studied. Our results indicated that Met-RANTES-treated mice had less behavioral hypersensitivity after partial sciatic nerve ligation. Macrophage infiltration, pro-inflammatory cytokine (TNFα, IL-1ß, IL-6, and IFNγ) protein secretion, and enkephalin, ß-endorphin, and dynorphin mRNA expression in damaged nerves following partial sciatic nerve ligation were significantly decreased, and anti-inflammatory cytokine (IL-10) protein was significantly increased in Met-RANTES-treated mice. These results suggest that CCL5 is capable of regulating the microenvironment that controls behavioral hypersensitivity at the level of the peripheral injured site in a murine chronic neuropathic pain model. PERSPECTIVE: The present study identifies the potent pro-inflammatory potential of CCL5 and verifies the possible role of selective CCL5 receptor inhibitor in a murine neuropathic pain model.

Pretreatment with small-dose ketamine reduces withdrawal movements associated with injection of rocuronium in pediatric patients.

UNLABELLED: We evaluated the pretreatment of small-dose of ketamine or normal saline in the reduction of withdrawal movements induced by rocuronium injection. One-hundred pediatric patients (aged 1-6 yr) were randomly assigned into 2 groups. A 22-gauge IV cannula was inserted into the dorsum of the hand, and ketamine 0.2 mg/kg or normal saline was given, followed by a 5 mg/kg thiopental injection 10 s later. IV rocuronium (0.8 mg/kg) was injected over 5 s. The patient's response to rocuronium injection was graded by using a four-point scale in a double-blinded manner. We observed that the incidence of withdrawal movements was 83% in the saline group and 27% in patients pretreated with ketamine (P < 0.05). Some patients in both groups developed skin erythema at the site of injection. We conclude that pretreatment with small-dose ketamine significantly attenuates withdrawal movements associated with IV injection of rocuronium in pediatric patients anesthetized with thiopental. IMPLICATIONS: Pretreatment with small-dose ketamine 0.2 mg/kg provides a simple and safe means of reducing the incidence of withdrawal movements induced by the injection of rocuronium, a short-acting nondepolarizing muscle relaxant.