Acute Consumption of Resistant Starch Reduces Food Intake but Has No Effect on Appetite Ratings in Healthy Subjects.

Previous studies have shown the benefits of native banana starch (NBS) supplementation in improving glucose metabolism and reducing body weight (BW) in humans. However, the effect of this starch on appetite regulation is unknown. The aim of this study was to examine the effects of NBS rich resistant starch on subjective measurements of appetite, energy intake, and appetite hormones in healthy subjects. Postprandial glucose and insulin responses were also assessed. In a randomized, single-blind, crossover study, 28 healthy young subjects consumed a beverage containing either 40 g of NBS or 40 g of digestible corn starch (DCS) on two separate occasions. Effects on appetite were estimated using visual analogue scales (VAS) and satiety hormone responses. At the end of the intervention, participants were provided with a pre-weighed ad libitum homogeneous test meal. After a washout period of 1 week, subjects received the alternative treatment. NBS supplementation induced a reduction in food intake, glucose area under the curve (AUC)-180 min, and insulin AUC-180 min. However, there was no associated effect on the subjective appetite ratings or gut hormones. NBS supplementation may help to reduce meal size and control BW.

Blockade of peripheral and spinal Na+/H+ exchanger increases formalin-induced long-lasting mechanical allodynia and hyperalgesia in rats.

The Na(+)/H(+) exchanger (NHE) is involved in the regulation of intracellular pH and volume by mediating the electroneutral transport of H(+) against an influx of Na(+) ions. Since NHE1 regulates pH in neurons and astrocytes and it is expressed in nociceptive nerve fibers, it is likely that NHE may modulate neuronal excitability and pain transmission. The purpose of this study was to assess the participation of peripheral and spinal NHE in the secondary allodynia/hyperalgesia induced by formalin. In addition, we determined whether formalin injection modifies the expression of NHE1 in lumbar dorsal root ganglia (DRG) and dorsal spinal cord. Subcutaneous injection of 0.5% formalin into the dorsal surface of the hind paw produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-lasting bilateral secondary mechanical allodynia/hyperalgesia. Peripheral and intrathecal pre-treatment (-10min) with selective NHE inhibitors 5-(N,N-dimethyl)amiloride hydrochloride (DMA, 0.3-30µM), 5-(N-ethyl-N-isopropyl)amiloride (EIPA, 0.3-30µM) and [1-(quinolin-5-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl] guanidine dihydrochloride (zoniporide, 0.03-3µM) significantly increased 0.5% formalin-induced bilateral long-lasting secondary allodynia/hyperalgesia. Contrariwise, local peripheral or intrathecal post-treatment (day 6 postinjection) with these NHE inhibitors did not affect formalin-induced nociceptive behaviors. Formalin injection reduced NHE1 expression in ipsilateral and contralateral spinal dorsal horns from day 1 to 12. In addition, formalin diminished NHE1 protein expression in DRG at day 12. These results suggest that NHE1 plays a role in pain processing at peripheral and spinal levels in formalin-induced long-lasting nociceptive behaviors. Additionally, these results suggest that proteins involved in pH regulation could be targets for the development of new analgesic drugs.

Sildenafil and glyceryl trinitrate reduce tactile allodynia in streptozotocin-injected rats.

The possible antiallodynic effect of phosphodiesterase 5 inhibitor sildenafil and nitric oxide donor glyceryl trinitrate as well as the changes in phosphodiesterase 5A2 mRNA expression in dorsal root ganglion and spinal cord of allodynic diabetic rats was assessed. Diabetes was induced by streptozotocin (50mg/kg, i.p.) in male Wistar rats. Streptozotocin injection produced hyperlglycemia, polydipsia, polyphagia and polyuria as well as long-term tactile allodynia (12 weeks) and a reduction of phosphodiesterase 5A2 mRNA expression in spinal cord of diabetic rats. Systemic administration of sildenafil (1-5.6 mg/kg, i.p.) reduced tactile allodynia in a dose-dependent manner in diabetic rats. Likewise, glyceryl trinitrate patches (0.2mg/h) also reduced tactile allodynia in diabetic rats. Moreover, both drugs reversed streptozotocin-induced phosphodiesterase 5A2 mRNA expression reduction. Our results indicate that glyceryl trinitrate and sildenafil reduce tactile allodynia in diabetic rats suggesting that nitric oxide and cyclic GMP supply is an important step in their mechanism of action of these drugs in diabetic animals. Data suggest that nitric oxide donors (as glyceryl trinitrate) and drugs which increase cyclic GMP levels (as sildenafil) could have a role in the pharmacotherapy of tactile allodynia in diabetic patients.

Role of opioid receptors in the reduction of formalin-induced secondary allodynia and hyperalgesia in rats.

This study assesses the effects of peripheral or intrathecal pre-treatment or post-treatment with micro, delta, kappa and nociceptin/orphanin FQ (NOP) opioid receptor agonists (morphine, U-50488 [trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide hydrochloride], DADLE [D-Ala2-Leu5-enkephalin] and nociceptin, respectively) on formalin-induced secondary mechanical allodynia and hyperalgesia in rats. 1% Formalin injection produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term tactile secondary allodynia and hyperalgesia. Neither peripheral (into the formalin-injected paw) nor intrathecal morphine post-treatment reversed formalin-induced secondary allodynia and hyperalgesia. In contrast, morphine pre-treatment prevented the development of these pain behaviors. Intrathecal and peripheral post- but not pre-treatment with U-50488 or DADLE significantly reduced secondary allodynia and hyperalgesia. Interestingly, nociceptin reduced both pain behaviors regardless of the administration site or treatment time. Local antinociceptive effects of morphine, DADLE, U-50488 or nociceptin were blocked by naltrexone, naltrindole, 5-guanidinonaltrindole and [Nphe(1)]nociceptin(1-13)NH(2), respectively. These results suggest that the long-term nociceptive behaviors induced by formalin are differentially modulated by selective opioid receptor agonists. In addition, data suggest that peripheral and spinal delta and kappa opioid receptors are important when nociceptive behaviors are established. In contrast, micro opioid receptors are more important at the beginning of the injury when the sensory system has not changed. NOP receptors participate diminishing both the development and maintenance of nociceptive behaviors. Results suggest that a barrage of afferent input induced by formalin injection initiates a long-term differential change in peripheral and spinal processing that affect the efficacy of opioid receptor agonists.

Synergistic antiallodynic interaction between gabapentin or carbamazepine and either benfotiamine or cyanocobalamin in neuropathic rats.

Anticonvulsants, including gabapentin and carbamazepine, have shown activity against several types of neuropathic pain; however, they have limiting side effects that may minimize their use. In this study the possible synergistic interaction between anticonvulsants and benfotiamine or cyanocobalamin on spinal nerve ligation-induced tactile allodynia was assessed. Oral administration of gabapentin (15-300 mg/kg), carbamazepine (10-300 mg/kg), benfotiamine (30-600 mg/kg) or cyanocobalamin (0.3-6.0 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with gabapentin 300 mg/kg (approximately 70%), carbamazepine 300 mg/kg (approximately 66%), benfotiamine 600 mg/kg (approximately 51%) and cyanocobalamin 6 mg/kg (approximately 59%). At the highest tested doses, gabapentin, but not carbamazepine, benfotiamine or cyanocobalamin, significantly reduced motor coordination. Coadministration of gabapentin or carbamazepine with benfotiamine or cyanocobalamin in a fixed ratio markedly reduced spinal nerve ligation-induced tactile allodynia, showing a synergistic interaction between anticonvulsants and B vitamins. Data indicate that combinations of anticonvulsants with benfotiamine or cyanocobalamin are able to reduce tactile allodynia without affecting motor coordination in rats, and suggest the possible clinical use of these combinations in the treatment of neuropathic pain in humans.

Subcutaneous, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia in the rat.

The purpose of this study was to assess the possible antiallodynic effect of asimadoline ([N-methyl-N-[1S)-1-phenyl)-2-(13S))-3-hydroxypyrrolidine-1-yl)-ethyl]-2,2-diphenylacetamide HCl]) and ICI-20448 ([2-[3-(1-(3,4-Dichlorophenyl-N-methylacetamido)-2-pyrrolidinoethyl)-phenoxy]acetic acid HCl]), two peripheral selective kappa opioid receptor agonists, after subcutaneous, spinal and periaqueductal grey administration to neuropathic rats. Twelve days after spinal nerve ligation tactile allodynia was observed, along with an increase in kappa opioid receptor mRNA expression in dorsal root ganglion and dorsal horn spinal cord. A non-significant increase in periaqueductal grey was also seen. Subcutaneous (s.c.) administration of asimadoline and ICI-204448 (1-30 mg/kg) dose-dependently reduced tactile allodynia. This effect was partially blocked by s.c., but not intrathecal, naloxone. Moreover, intrathecal administration of asimadoline or ICI-204448 (1-30 mug) reduced tactile allodynia in a dose-dependent manner and this effect was completely blocked by intrathecal naloxone. Microinjection of both kappa opioid receptor agonists (3-30 mug) into periaqueductal grey also produced a naloxone-sensitive antiallodynic effect in rats. Our results indicate that systemic, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia. This effect may be a consequence of an increase in kappa opioid receptor mRNA expression in dorsal root ganglion, dorsal horn spinal cord and, to some extent, in periaqueductal grey. Finally, our data suggest that these drugs could be useful to treat neuropathic pain in human beings.