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Background Epidurals may be challenging in neonatal patients due to technical difficulties relating to insertion and the risk of local anaesthesia toxicity. The use of wound catheters with an infusion of local anaesthetic has been shown to be well tolerated in adults and older children. There are few data concerning wound catheter techniques in neonatal patients. Objectives The primary aim of this study was to analyse plasma levels of levobupivacaine associated with continuous wound infiltration via a catheter following neonatal surgical procedures. Secondary parameters, including the quality of postoperative analgesia and wound healing, were also noted. Design A prospective, observational study. Setting Paediatric ICU at the Karolinska University Hospital, Stockholm, Sweden, from March 2008 to December 2010. Patients Twenty newborn infants (median weight 3.48 kg) scheduled for major abdominal or thoracic surgery were included. Exclusion criteria were known or suspected hepatic dysfunction. Before skin closure, a subcutaneous catheter was inserted into the wound followed by a 0.5 mg kg(-1) bolus of levobupivacaine (0.125%, 0.4 ml kg(-1)) through the catheter. A continuous infusion was started 20 to 30 min later at a rate of 0.2 mg kg(-1)h(-1) (0.16 ml kg(-1) h(-1)). Main outcome measures Plasma concentrations of levobupivacaine (total and unbound) at 12, 24, 48 and 72 h postoperatively. Morphine consumption, pain scores and wound healing were also analysed. Results Median concentrations of unbound and total levobupivacaine at 72 h were 0.018 and 1.305 μg ml(-1), respectively. In 18 out of 20 infants [90%; 95% confidence interval (CI) 68.3 to 98.8], the unbound plasma concentration of levobupivacaine remained relatively stable and below 0.05 μg ml(-1) throughout the 72 h observation period. Pain scores and morphine consumption levels were low. All wounds except one healed within 10 days. Conclusion The studied infusion regimen was associated with plasma levels of levobupivacaine well below those associated with toxicity. Adequate wound healing, low pain scores and a reduced need for opioids were also noted.

The gene expression of cholecystokinin (CCK), a neuropeptide with anti-opioid properties, has been reported to be up-regulated in some primary sensory neurons after a peripheral nerve lesion. We have recently demonstrated that the up-regulation of CCK mRNA is not accompanied by an increased potassium-evoked release of CCK-like immunoreactivity (CCK-LI) 2-4 weeks after a complete transection of the sciatic nerve. The potassium-evoked release of CCK-LI at earlier and later time points has, however, not been studied. The aim of the present in vivo microdialysis study was to monitor how the basal and stimulated extracellular level of CCK in the dorsal horn of the spinal cord is affected at various time points after a complete transection of the sciatic nerve (axotomy). During the first week after transection of the sciatic nerve a tendency towards an elevation of the potassium-induced (100 mM in the perfusion fluid) release of spinal CCK-LI was observed. In contrast, no potassium-induced release of CCK-LI could be detected 2-3 weeks and 2 months after axotomy. No significant effect was observed on the basal extracellular levels of CCK-LI in the dorsal horn. The present study provides further support for the notion that the adaptive changes in the dorsal horn 2 weeks and later after a deafferentiation injury do not include an increased release of CCK.

The anterior cingulate cortex (ACC) is a limbic region with a high density of cholecystokinin (CCK) immunoreactivity, that has been suggested to be of importance for the affective and emotional component of pain. In the present microdialysis study, performed in the awake rat, we demonstrate a bilateral 4- to 6-fold increase of the potassium-induced release of CCK-like immunoreactivity (CCK-LI) in the ACC 2-3 weeks after a unilateral transection of the sciatic nerve (axotomy), an animal model of phantom limb or deafferentiation pain. Considering the implication of CCK in pain modulation and anxiety, we suggest that an altered activity of CCK containing neurons in the ACC may be of importance for the affective component of certain pain conditions.

OBJECTIVE The aim of the present study is to monitor the extracellular gamma-aminobutyric acid (GABA) levels in the lumbar dorsal horn of allodynic rats, which respond to spinal cord stimulation (SCS) with a normalization of the tactile withdrawal threshold. In addition, we monitored the GABA levels in nonresponding and sham-stimulated rats. METHODS Partial constriction injury of the sciatic nerve was performed, and a permanent electrode for SCS was inserted into the spinal canal. The response to SCS was assessed with von Frey hairs in awake animals. Later, microdialysis was performed in the dorsal horn of the spinal cord under halothane anesthesia. The concentration of GABA in the microdialysate was assessed by high-performance liquid chromatography. RESULTS Extracellular GABA levels in rats with sciatic nerve lesions and allodynia (2.3 +/- 0.5 nmol/L) were significantly lower (P < 0.001) than in control rats with intact sciatic nerves (8.1 +/- 1.0 nmol/L), whereas only slightly decreased GABA levels (5.7 +/- 1.1 nmol/L) were detected in nonallodynic rats with sciatic nerve lesions. In the allodynic rats, which respond to SCS by a normalization of the tactile withdrawal threshold, significantly (P < 0.001) increased GABA levels (6.7 +/- 2.3 nmol/L) were detected after SCS. In contrast, neither the allodynic rats, which did not respond to SCS, nor the sham-stimulated allodynic rats displayed increased GABA levels in response to stimulation. CONCLUSION Our results indicate that the development of allodynia, a common symptom in neuropathic pain states, may be linked to a decreased spinal release of GABA. We suggest that an SCS-induced release of GABA could be important for the suppression of allodynia observed in rats after SCS. Similar mechanisms could also be involved in the SCS-induced alleviation of pain in patients with peripheral neuropathy.

The mechanism underlying the beneficial effect of electrical stimulation of the posterior surface of the spinal cord in chronic pain states are unknown. The prolonged pain relief following a short stimulation period is believed to imply the activation of long-lasting neurochemical processes, mainly in the spinal cord, but possibly also involving other parts of the central nervous system. Previous studies have demonstrated that substance P and serotonin are released in the cat dorsal horn during spinal cord stimulation (SCS) with electrical parameters similar to those used in the clinic. However, gamma-aminobutyric acid (GABA) has also been hypothesized to play a role in the effect of SCS, but there have been no studies of the possible effects of SCS on GABA release. The authors applied SCS to anesthetized rats and monitored the extracellular concentration of GABA in the lumbar dorsal horns by microdialysis and a sensitive reverse-phase high-performance liquid chromatography technique. After 30 minutes of SCS, the GABA level increased significantly (by almost 270%) in comparison with the basal level recorded before stimulation, from 3.6 +/- 1.0 nmol/L to 13.1 +/- 2.2 nmol/L (mean +/- the standard error of the mean; P < 0.05). The peak release was delayed and appeared in the 30-minute fraction collected after stimulation. Also, perfusion of the dialysis probes with potassium (100 mmol/L) induced an increase of the GABA level. In control experiments without electrical stimulation, slowly decreasing GABA levels were observed throughout the experiments. The present results may suggest an involvement of GABA in the mechanism of SCS-induced pain relief.(ABSTRACT TRUNCATED AT 250 WORDS)