Treatment of pain post-brachial plexus injury using high-frequency spinal cord stimulation.

PURPOSE: Brachial plexopathy can sometimes cause severe chronic pain. There are many possible treatments for such neuropathic pain, including neuromodulation. However, rigorous scientific evidence on the usefulness of spinal cord stimulation (SCS) is still scarce. Here, we report the use of high-frequency (10 kHz) SCS (HFSCS) in a patient with brachial plexus injury (root avulsion). OBJECTIVE: To assess the efficacy of HFSCS in root avulsion and to investigate the putative neurophysiological mechanisms of HFSCS. METHODS: A 32-year-old woman visited our center following an iatrogenic brachial plexus injury. She underwent traditional, paresthesia-inducing, tonic SCS with cervical lead placement. She reported that stimulation-induced paresthesia was uncomfortable, without any pain reduction. After the successful trial of HFSCS, the patient was assessed at 1 month (T1) and 6 months (T6) after HFSCS implantation with pain and quality of life (QoL) scales. Moreover, she underwent a neurophysiological assessment (somatosensory evoked potentials [SEPs], reciprocal inhibition [RI], pain-motor integration [PMI], and the habituation of intraepidermal electrical stimulation-induced evoked potentials [IEPs]) with the stimulator switched on and switched off at T6. RESULTS: The patient reported 100% paresthesia-free pain relief, a consistent improvement of QoL, and a complete discontinuation of her previous pain treatment at T1 and T6. Moreover, we found suppression of SEPs, restored habituation of IEPs, and strengthening of RI and PMI. CONCLUSION: This is the first report to illustrate the usefulness and safety of HFSCS for treating root avulsion in a patient with failed tonic SCS. Our data indicate that HFSCS may either block large-diameter fibers or stimulate medium-/small-diameter fibers, thus inducing analgesia without paresthesia, probably by reducing the activation of the wide-dynamic-range neurons. Moreover, HFSCS seems to modulate spinal inhibitory mechanisms and the descending corticospinal inhibitory output. Thus, HFSCS can be an effective option for treating refractory pain following root avulsion.

Use of polyurethane foam inside plaster casts to prevent the onset of heel sores in the population at risk. A controlled clinical study.

AIM: The aim of this study was to test the effectiveness of polyurethane foam in contact with the heel inside a plaster cast to decrease the rate of pressure sores in the population at most risk. BACKGROUND: The rate of pressure sores caused by the plaster cast is reported to be 14-15% in the paediatric population, 33.3% in patients having undergone chemotherapy for bone tumours and 43% in orthopaedic patients who already have sore skin when the cast is applied (grade 1 lesion) to the heel. DESIGN: Controlled clinical trial. METHODS: From November 2007-January 2009, all consecutive subjects requiring lower limb casts having undergone chemotherapy and/or presenting heel soreness received polyurethane foam in contact with the skin of the heel before applying the cast. The results were compared with those of patients with the same risk factors but were not administered the foam and were enrolled from May 2005-August 2006. RESULTS: In total, 156 patients were enrolled, 85 in the control group and 71 in the experimental group. In the experimental group, 2 of the 56 patients (3.6%) with sore skin developed a pressure sore compared with 21 of 49 (42.9%) in the control group without polyurethane foam (p < 0.0005). In the experimental group, one of the 24 patients (4.2%) patients undergoing chemotherapy developed a pressure sore compared with 18 of 54 (33.3%) in the control group (p = 0.005). CONCLUSIONS: Placing polyurethane foam in contact with the skin of the heel inside a plaster cast prevents the formation of pressure sores. RELEVANCE TO CLINICAL PRACTICE: This study provides evidence that using polyurethane foam to prevent sores even inside plaster casts in populations at most risk is a simple and cost-effective strategy and decreases the discomfort, pain and risks in these patients.

Melanocortin 4 receptor stimulation decreases pancreatitis severity in rats by activation of the cholinergic anti-inflammatory pathway.

OBJECTIVE: Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure. Melanocortin peptides have been successfully used in experimental models of organ failure and shock, and their protective effect occurs through the activation of a vagus nerve-mediated cholinergic anti-inflammatory pathway by acting at brain melanocortin 4 receptors. In the light of these observations, we studied the effects of the selective melanocortin 4 receptor agonist RO27-3225 in an experimental model of cerulein-induced pancreatitis. DESIGN: Randomized experiment. SETTING: Research laboratory at a university hospital. SUBJECT: Experimental pancreatitis in rats. INTERVENTIONS: Acute pancreatitis was induced in male Sprague-Dawley rats by intraperitoneal injections of cerulein (80 µg/kg, four injections at hourly intervals). Before pancreatitis induction, groups of animals were subjected to bilateral cervical vagotomy, pretreated with the nicotinic acetylcholine receptor antagonist chlorisondamine or the selective melanocortin 4 receptor antagonist HS024, or not pretreated. Thirty minutes after the first cerulein injection, rats were intraperitoneally treated with a nanomolar dose of RO27-3225 or vehicle. Some experimental groups were prepared for neural efferent activity recording along the vagus nerve starting 30 mins after treatment with RO27-3225 or vehicle, and for a 30-min period. MEASUREMENTS AND MAIN RESULTS: Serum lipase and amylase activity, tumor necrosis factor-α and interleukin-6 expression, pancreatic myeloperoxidase activity, and histologic damage were evaluated; neural efferent activity of vagal fibers was also assessed. RO27-3225 reduced cerulein-induced serum lipase and amylase activity, blunted the expression of tumor necrosis factor-α and interleukin-6, abated the increase in pancreatic myeloperoxidase activity, and protected against histologic damage. Furthermore, RO27-3225 markedly increased neural efferent activity along the vagus nerve. Vagotomy, chlorisondamine, and HS024 abated these protective effects of RO27-3225. CONCLUSIONS: Our data show that melanocortin 4 receptor agonists reduce pancreatitis severity through the activation of the cholinergic anti-inflammatory pathway. These findings could be of particular interest in the clinical setting.

Melanocortins protect against multiple organ dysfunction syndrome in mice.

BACKGROUND AND PURPOSE: Melanocortins reverse circulatory shock and improve survival by counteracting the systemic inflammatory response, and through the activation of the vagus nerve-mediated cholinergic anti-inflammatory pathway. To gain insight into the potential therapeutic value of melanocortins against multiple organ damage following systemic inflammatory response, here we investigated the effects of the melanocortin analogue [Nle4 D-Phe7]α-MSH (NDP-α-MSH) in a widely used murine model of multiple organ dysfunction syndrome (MODS). EXPERIMENTAL APPROACH: MODS was induced in mice by a single intraperitoneal injection of lipopolysaccharide followed, 6 days later (= day 0), by zymosan. After MODS or sham MODS induction, animals were randomized to receive intraperitoneally NDP-α-MSH (340 µg·kg⁻¹ day) or saline for up to 16 days. Additional groups of MODS mice were concomitantly treated with the melanocortin MC4 receptor antagonist HS024, or the nicotinic acetylcholine receptor antagonist chlorisondamine, and NDP-α-MSH. KEY RESULTS: At day 7, in the liver and lung NDP-α-MSH, significantly reduced mRNA expression of tumour necrosis factor-α (TNF-α), increased mRNA expression of interleukin-10 and improved the histological picture, as well as reduced TNF-α plasma levels; furthermore, NDP-α-MSH dose-dependently increased survival rate, as assessed throughout the 16 day observation period. HS024 and chlorisondamine prevented all the beneficial effects of NDP-α-MSH in MODS mice. CONCLUSIONS AND IMPLICATIONS: These data indicate that NDP-α-MSH protects against experimental MODS by counteracting the systemic inflammatory response, probably through brain MC4 receptor-triggered activation of the cholinergic anti-inflammatory pathway. These findings reveal previously undescribed effects of melanocortins and could have clinical relevance in the MODS setting.