Yoga: Can it be integrated with treatment of neuropathic pain?

BACKGROUND: Neuropathic pain (NP) is a debilitating condition that may result from spinal cord injury (SCI). Nearly 75% of all SCI results in NP affecting 17,000 new individuals in the United States every year, and an estimated 7-10% of people worldwide. It is caused by damaged or dysfunctional nerve fibers sending aberrant signals to pain centers in the central nervous system causing severe pain that affects daily life and routine. The mechanisms underlying NP are not fully understood, making treatment difficult. Identification of specific molecular pathways that are involved in pain syndromes and finding effective treatments has become a major priority in current SCI research. Yoga has therapeutic applications may prove beneficial in treating subjects suffering chronically with SCI induced NP, chronic back and associated pains if necessary experimental data is generated. SUMMARY: This review aims to discuss the implications of various mechanistic approaches of yoga which can be tested by new study designs around various nociceptive molecules including matrix metalloproteinases (MMPs), cation-dependent chloride transporter (NKCC1) etc in SCI induced NP patients. KEY MESSAGES: Thus, yogic practices could be used in managing SCI induced NP pain by regulating the action of various mechanisms and its associated molecules. Modern prescriptive treatment strategies combined with alternative approaches like yoga should be used in rehabilitation centers and clinics in order to ameliorate chronic NP. We recommend practical considerations of careful yoga practice as part of an integrative medicine approach for NP associated with SCI.

Early versus delayed cord clamping in small for gestational age infants and iron stores at 3 months of age - a randomized controlled trial.

BACKGROUND: Delayed cord clamping is the standard of care in infants not requiring resuscitation; however effects of cord clamping strategies have not been evaluated systematically in small for gestational age (SGA) infants. The primary objective was to compare effects of delayed cord clamping (DCC) and early cord clamping (ECC) on serum ferritin at 3 months in SGA infants born at ≥35 weeks. The secondary objectives were to compare hematological parameters, clinical outcomes in neonatal period and growth at 3 months of age. METHODS: All eligible infants with fetal growth restriction were randomized to two groups, DCC at 60 s or ECC group in which the cord was clamped immediately after birth. RESULTS: Total of 142 infants underwent randomization and subsequently 113 infants underwent definite inclusion. At 3 months, the median (IQR) serum ferritin levels were higher in DCC group, compared to ECC; 86 ng/ml (43.35-134.75) vs 50.5 ng/ml (29.5-83.5), p = 0.01. Fewer infants had iron deficiency in DCC group compared to ECC group; 9 (23.6%) vs 21 (47.7%), p = 0.03 [NNT being 4; 95% CI (2-25)].The proportion of infants with polycythemia was significantly higher in DCC group; 23 (41.81) % vs 12 (20.6%), p = 0.01. There was no difference in proportion of infants with symptomatic polycythemia or those who underwent partial exchange transfusions. Clinical outcomes and mortality were similar. CONCLUSIONS: DCC improves iron stores in SGA infants ≥35 weeks at 3 months of age without increasing the risk of symptomatic polycythemia, need for partial exchange transfusions or morbidities associated with polycythemia. TRIAL REGISTRATION: Our trial was retrospectively registered on 29th May 2015 through Clinical trials registry India. Registration number: CTRI 2015/05/005828 .

Comparative Morphometry of the Wisconsin Miniature SwineTM Thoracic Spine for Modeling Human Spine in Translational Spinal Cord Injury Research.

BACKGROUND/AIMS: Spine and spinal cord pathologies and associated neuropathic pain are among the most complex medical disorders to treat. While rodent models are widely used in spine and spinal cord research and have provided valuable insight into pathophysiological mechanisms, these models offer limited translatability. Thus, studies in rodent models have not led to the development of clinically effective therapies. More recently, swine has become a favored model for spine research because of the high congruency of the species to humans with respect to spine and spinal cord anatomy, vasculature, and immune responses. However, conventional breeds of swine commonly used in these studies present practical and translational hurdles due to their rapid growth toward weights well above those of humans. METHODS: In the current study, we evaluated the suitability of a human-sized breed of swine developed at the University of Wisconsin-Madison, the Wisconsin Miniature SwineTM (WMSTM), in the context of thoracic spine morphometry for use in research to overcome limitations of conventional swine breeds. The morphometry of thoracic vertebrae (T1-T15) of 5-6 months-old WMS was analyzed and compared to published values of human and conventional swine spines. RESULTS: The key finding of this study is that WMS spine more closely models the human spine for many of the measured vertebrae parameters, while being similar to conventional swine in respect to the other parameters. CONCLUSION: WMS provides an improvement over conventional swine for use in translational spinal cord injury studies, particularly long-term ones, because of its slower rate of growth and its maximum growth being limited to human weight and size.

Folic Acid Modulates Matrix Metalloproteinase-2 Expression, Alleviates Neuropathic Pain, and Improves Functional Recovery in Spinal Cord-Injured Rats.

BACKGROUND: The molecular underpinnings of spinal cord injury (SCI) associated with neuropathic pain (NP) are unknown. Recent studies have demonstrated that matrix metalloproteinases (MMPs) such as MMP2 play a critical role in inducing NP following SCI. Promoter methylation of MMPs is known to suppress their transcription and reduce NP. In this context, it has been shown in rodents that folic acid (FA), an FDA approved dietary supplement and key methyl donor in the central nervous system (CNS), increases axonal regeneration and repair of injured CNS in part via methylation. PURPOSE: Based on above observations, in this study, we test whether FA could decrease MMP2 expression and thereby decrease SCI-induced NP. METHODS: Sprague-Dawley male rats weighing 250-270 g received contusion spinal cord injuries (cSCIs) with a custom spinal cord impactor device that drops a 10 g weight from a height of 12.5 mm. The injured rats received either i.p. injections of FA (80 µg/kg) or water (control) 3 days prior and 17 days post-cSCI (mid phase) or for 3 days pre-cSCI and 14 days post-cSCI ending on the 42nd day of cSCI (late phase). The functional neurological deficits due to cSCI were then assessed by Basso, Beattie, and Bresnahan (BBB) scores either on post-impaction days 0 through 18 post-cSCI (mid phase) or on days 0, 2, 7, 14, 21, 28, 35, and 42 (late phase). Baseline measurements were taken the day before starting treatments. Thermal hyperalgesia (TH) testing for pain was performed on 4 days pre-cSCI (baseline data) and on days 18, 21, 28, 35, and 42 post-cSCI. Following TH testing, animals were euthanized and spinal cords harvested for MMP-2 expression analysis. RESULT: The FA-treated groups showed higher BBB scores during mid phase (day 18) and in late phase (day 42) of injury compared to controls, suggesting enhanced functional recovery. There is a transient decline in TH in animals from the FA-treated group compared to controls when tested on days 18, 21, 28, and 35, indicative of a decrease in NP. However, when tested 25 days after stopping FA administration on day 42 of cSCI, no significant difference in TH was observed between FA-treated and control animals. Western blot analysis of the injured spinal cord from FA-treated animals showed significant decline in MMP2 expression compared to spinal cord samples from water-treated controls. CONCLUSION: Together, these data suggest that FA could alleviate NP and improve functional recovery post-SCI, possibly by reducing the expression of MMP2. Further studies will open up a novel and easy natural therapy, ideal for clinical translation with minimal side effects, for managing SCI-induced NP. Such studies might also throw light on a possible epigenetic mechanism in FA-induced recovery after SCI.

Translational Relevance of Swine Models of Spinal Cord Injury.

Spinal cord injury (SCI) is a physically and psychologically devastating clinical condition. The typical treatment regimens of decompressive surgery and rehabilitation therapy still leave many patients with permanent disability. The development of new therapies and devices can be accelerated if relevant translational animal models are more effectively used in pre-clinical stages. Swine is a highly relevant model for SCI research, especially with respect to spine and spinal cord anatomy, spine vasculature, immune responses to injury, and functional assessments. Several spine injury models have recently been developed for swine and are beginning to be used to evaluate new therapies. Swine models of SCI offer tremendous advantages for efficient translation of pre-clinical discoveries and the development of new therapies and devices. Future swine models will also be enhanced by advances in gene-editing technology to further elucidate the complex pathophysiology associated with SCI and provide a means to engineer specific spinal pathologies.

Plasmodium vivax malaria admissions and risk of mortality in a tertiary-care children's hospital in North India.

BACKGROUND: In 2010, there was an increase in the severity of malaria admissions to Kalawati Saran Children's Hospital, New Delhi and this report describes the morbidity and mortality profile. METHOD: A retrospective chart review of patients admitted with parasitologically confirmed malaria between January and December 2010. RESULTS: There were 156 cases: P. vivax 105 (67.3%), P. falciparum 39 (25%) and mixed infections 12 (7.7%). Thrombocytopenia (platelet count <150×10(9)/L) was present in 90 (85.7%) patients with P. vivax mono-infection. There were 91 (58.3%) patients with severe malaria: P. vivax mono-infection 46 (50.5%), P. falciparum mono-infection 35 (38.5%) and mixed 10 (11%). Severe anaemia and severe thrombocytopenia (platelet count <20×10(9)/L) were detected significantly more often in P. falciparum and P. vivax mono-infection, respectively. Complications including cerebral malaria, acute renal failure, shock, acute respiratory distress syndrome (ARDS) and multiple-organ dysfunction syndrome (MODS) were similar in both groups. The mortality rate of around 20% was similar in severe P. vivax and P. falciparum mono-infection. Risk of mortality in vivax malaria was highest in patients with ARDS followed by MODS and shock. CONCLUSION: Increased morbidity owing to P. vivax malaria was observed and risk of mortality was highest in patients with ARDS and MODS.

Hypertonic versus normal saline as initial fluid bolus in pediatric septic shock.

OBJECTIVE: To compare the efficacy of 3% saline and 0.9% saline infusion as initial resuscitative fluid therapy in children with septic shock. METHODS: Sixty children between 2 to 12 years of age with septic shock were randomized to receive normal saline or 3% saline as initial resuscitative fluid. Fluid resuscitation was done with 0.9% saline in boluses of 20 ml/kg, each bolus over a duration of 15 min with a maximum of 2 boluses. Fluid resuscitation with 3% saline was given as a single bolus of 15 ml/kg over 30 min. After initial fluid bolus completion, if hemodynamic stability was not achieved then further fluid boluses of 0.9% saline were given in volumes of 5-10 ml/kg guided by CVP. RESULTS: There were 30 patients in both the groups. Both the groups were identical with respect to age, gender, primary diagnosis, laboratory parameters, initial hemodynamic parameters and PRISM score at time of admission. The amount of total fluid bolus required for resuscitation was approximately half in the group who received 3% saline as compared to the group who received 0.9% saline. The use of vasopressor drugs, shock reversal time, ICU stay and mortality rate were similar in both the groups. No adverse effects related to fluid therapy were observed in any of the groups. CONCLUSIONS: Both normal saline and hypertonic saline were equally effective as resuscitation fluid with respect to restoration of hemodynamic stability, average duration of ICU stay and mortality. Hypertonic saline appears to be a promising fluid for resuscitation of septic shock.