Effect of chronic intake of sweet substance on nociceptive thresholds and feeding behavior of Rattus norvegicus (Rodentia, Muridae).

The investigation of the influence of sweetened food on feeding behavior targeted to non-sucrose nutrients as well as the sensitivity to painful stimuli in isolated and grouped animals is the aim of the present work. The tail withdrawal latencies in the tail-flick test (a spinal reflex) were measured before and immediately after the treatment with tap water or sucrose (62, 125 or 250 g/l). Our findings suggest that: (a) The analgesic effect of sucrose intake depends on the concentration of sucrose solution and on the time during which the solution is consumed; (b) the most effective concentration of sucrose followed by antinociceptive effect was the one of 250 g/l in both isolated and grouped animals; (c) considering the individually caged rats, the intake of sucrose in the highest concentration (250 g/l) was the smallest as compared with the consumption of sucrose in more diluted solutions (62.5 and 125 g/l), but this higher sweetened solution was followed by antinociception; (d) animals treated with concentrated sucrose solution ate smaller quantities of pellets than animals treated with tap water; (e) tonic intake of highly concentrated sweet substance seems to be crucial for the increase of the nociceptive threshold in our model of sweet substance-induced antinociception.

Effect of the blockade of mu1-opioid and 5HT2A-serotonergic/alpha1-noradrenergic receptors on sweet-substance-induced analgesia.

RATIONALE: Sweet-substance-induced analgesia has been widely studied, and the investigation of the neurotransmitters involved in this antinociceptive process is an important way for understanding the involvement of the neural system controlling this kind of antinociception. OBJECTIVE: The aim of this study was to investigate the involvement of opioid and monoaminergic systems in sweet-substance-induced analgesia. METHODS: The present work was carried out in an animal model with the aim of investigating whether acute (24 h) or chronic (14 days) intake of a sweet substance, such as sucrose (250 g/l), is followed by antinociception. Tail withdrawal latencies in the tail-flick test were measured before and immediately after this treatment. Immediately after the recording of baseline values, independent groups of rats were submitted to sucrose or tap-water intake and, after chronic treatment, they were pretreated with intraperitoneal administration of (1) naltrexone at 0.5, 1, 2 or 3 mg/kg; (2) naloxonazine at 5, 10, 20 or 30 mg/kg; (3) methysergide at 0.5, 1, 2 or 3 mg/kg; (4) ketanserin at 0.5, 1, 2 or 3 mg/kg; or (5) physiological saline. RESULTS: Naltrexone and methysergide at two major doses decreased sweet-substance-induced analgesia after chronic intake of a sweet substance. These effects were corroborated by peripheral administration of naloxonazine and ketanserin. CONCLUSIONS: These data give further evidence for: (a) the involvement of endogenous opioids and a mu1-opioid receptor in the sweet-substance-induced antinociception; (b) the involvement of monoamines and 5HT2A serotonergic/alpha1-noradrenergic receptors in the central regulation of the sweet-substance-produced analgesia.

Opioid neurotransmission in the post-ictal analgesia: involvement of mu(1)-opioid receptor.

Pentylenetetrazol (PTZ), a non-competitive antagonist that blocks GABA-mediated Cl(-) flux, was used in the present work to induce seizures in animals. The aim of this work is to study the neurochemical basis of the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test, in eight rats per group. Convulsions were followed by significative increase in the tail-flick latencies (TFL), for at least 120 min of the post-ictal period. Peripheral administration of naltrexone (5 mg/kg, 10 mg/kg and 20 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls. These data were corroborated with peripheral administration of naloxonazine (10 mg/kg and 20 mg/kg), a mu(1)-opioid blocker, in the same doses used for non-specific antagonist. These results indicate that endogenous opioids may be involved in the post-ictal analgesia. The involvement of mu(1)-opioid receptor was also considered.

Post-ictal analgesia: involvement of opioid, serotoninergic and cholinergic mechanisms.

The neural mechanisms involved in post-ictal analgesia remain to be elucidated. Pentylenetetrazol (PTZ) is used experimentally to induce seizure in animal subjects. This non-competitive antagonist blocks GABA-mediated Cl(-) flux. The aim of this work is to study the neurochemical basis of the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test, in eight rats per group. Convulsions were followed by significant increase in the tail-flick latencies (TFL), at least for 30 min of the post-ictal period. Peripheral administration of naloxone (5 mg/kg and 10 mg/kg), atropine (1 mg/kg and 5 mg/kg), methysergide (1 mg/kg and 5 mg/kg) and ketanserine (1 mg/kg and 2 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls. However, while naloxone antagonized analgesia 15 and 25 min post convulsions, the other drugs caused a blockade of the post-ictal analgesia in a relatively greater period of time. These results indicate that endogenous opioids, serotonin and acetylcholine may be involved in post-ictal analgesia.

Sucrose ingestion causes opioid analgesia.

The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l) for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex) were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean +/- SEM, N = 12) for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 +/- 0.04, 0.10 +/- 0.05, 0.15 +/- 0.08 and 0.49 +/- 0.07, respectively. One-way ANOVA indicated a significant difference (F(3, 47) = 9.521, P < 0.001) and the Tukey multiple comparison test (P < 0.05) showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7) receiving sucrose exhibited an analgesia index of 0.20 +/- 0.10 while rats receiving only sucrose (N = 7) had an index of 0.68 +/- 0.11 (t = 0.254, 10 degrees of freedom, P < 0.03). This result indicates that the analgesic effect of sucrose depends on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.

Sucrose ingestion causes opioid analgesia

The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/I) for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex) were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean + SEM,N = 12) for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 + 0.04, 0.10 + 0.05, 0.15 + 0.08 and 0.49 + 0.07, respectively. One-way ANOVA indicated a significant difference (F(3,47) = 9.521, P<0.001) and the Tukey multiple comparison test (P<0.05) showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7) receiving sucrose exhibited an analgesia index of 0.20 + 0.10 while rats receiving only sucrose (n = 7) had an index of 0.68 + 0.11 (t=0.254, 10 degreed of freedom, P<0.03). This result indicates that the analgesic effect of sucrose depens on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.