Massage for mechanical neck disorders.

BACKGROUND: Mechanical neck disorders (MND) are common, disabling and costly. Massage is a commonly used modality for the treatment of neck pain. OBJECTIVES: To assess the effects of massage on pain, function, patient satisfaction and cost of care in adults with neck pain. To document adverse effects of treatment. SEARCH STRATEGY: Cochrane CENTRAL, MEDLINE, EMBASE, MANTIS, CINAHL, and ICL databases were electronically searched, without language restriction, from their inception to September 2004 SELECTION CRITERIA: Studies using random or quasi-random assignment were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently conducted citation identification, study selection, data abstraction and methodological quality assessment. Using a random-effects model, we calculated the relative risk and standardized mean difference. MAIN RESULTS: Nineteen trials met the inclusion criteria. Overall, the methodological quality was low, with 12/19 assessed as low-quality studies. Trials could not be statistically pooled because of heterogeneity in treatment and control groups. Therefore, a levels-of-evidence approach was used to synthesize results. Assessment of the clinical applicability of the trials showed that the participant characteristics were well reported, but neither the descriptions of the massage intervention nor the credentials or experience of the massage professionals were well reported. Six trials examined massage as a stand-alone treatment. The results were inconsistent. Of the 14 trials that used massage as part of a multimodal intervention, none were designed such that the relative contribution of massage could be ascertained. Therefore, the role of massage in multimodal treatments remains unclear. AUTHORS' CONCLUSIONS: No recommendations for practice can be made at this time because the effectiveness of massage for neck pain remains uncertain. Pilot studies are needed to characterize massage treatment (frequency, duration, number of sessions, and massage technique) and establish the optimal treatment to be used in subsequent larger trials that examine the effect of massage as either a stand-alone treatment or part of a multimodal intervention. For multimodal interventions, factorial designs are needed to determine the relative contribution of massage. Future reports of trials should improve reporting of the concealment of allocation, blinding of outcome assessor, adverse events and massage characteristics. Standards of reporting for massage interventions, similar to CONSORT, are needed. Both short- and long-term follow-up are needed.

Diurnal changes in paraventricular hypothalamic alpha1 and alpha2-adrenoceptors and food intake in rats.

The prominent feeding rhythm evident in rats may reflect circadian variation in activity of feeding-relevant adrenoceptors within the hypothalamic paraventricular nucleus (PVN). In the present study, separate groups of rats were sacrificed at six time points (ZT0, ZT4, ZT8, ZT12, ZT16, ZT20) over a diurnal cycle. Food intakes were recorded during the 4-h period prior to sacrifice in each group. Brain sections were incubated with either an alpha1-adrenoceptor ligand (3H)-prazosin [(3H)-PRZ] or an alpha2-adrenoceptor ligand (3H) para-aminoclonidine [(3H)-PAC] prior to autoradiography analyses. Binding of (3H)-PRZ within the PVN varied as a function of the diurnal cycle, with significantly greater binding evident during the light phase of ZT0 (first 4 h of the light phase) and at ZT4, compared to nadir binding during the dark phase at ZT16 (first 4 h of the dark phase). Binding of (3H)-PAC within the PVN also varied as a function of the diurnal cycle, with significantly greater binding evident during the first 8 h of the dark phase (ZT16 and ZT20) than during the light phase. Food intake and alpha1-adrenergic binding were inversely related across the diurnal cycle. These results support the hypothesis that PVN adrenergic systems may be organized in an antagonistic fashion so as to modulate feeding in the rat.

Expression of Fos immunoreactivity in rat brain during dehydration: effect of duration and timing of water deprivation.

Water deprivation induces expression of the immediate early gene c-fos in specific brain regions, most likely as a result of the activation of cells that are responsive to changes in osmolality and/or blood volume. We hypothesized that the magnitude of c-fos expression would be a function of both the duration of water deprivation and the time of day at which the deprivation started. This study was designed to examine the pattern of Fos-like immunoreactivity (FLI) following water deprivation in rats under normal light/dark conditions (nLD) and reverse light/dark conditions (rLD). Rats were deprived of water but not food either for 0, 5, 16, 24 or 48 h. As expected, hematocrit ratio (HCT), osmolality (OSM), plasma renin activity (PRA) and weight loss increased as a function of duration of water deprivation. In non-deprived rats (0 h), very little FLI was observed in most brain regions. The number of cells showing FLI increased with duration of water deprivation in the supraoptic nucleus (SON), paraventricular nucleus (PVN), organum vasculosum laminae terminalis (OVLT), median preoptic nucleus (MnPO) and subfornical organ (SFO) in both nLD and rLD conditions. However, the pattern of FLI differed between nLD and rLD conditions. Compared to corresponding nLD groups after 5 or 24-h water deprivation, rLD groups had significantly more FLI in SON and PVN, and higher PRA and HCT. Also, weight loss and FLI in the MnPO were greater after 5 h, and FLI in the SFO was greater after 24 h under rLD compared to nLD conditions. Our findings indicate that the magnitude of c-fos expression, and change in weight and plasma parameters were a function of both the duration of water deprivation and the time of day at which the deprivation started. This may result from ingestion of food early in the deprivation periods during the rLD tests, thus producing greater change in osmolality and blood volume.

Aging and fluid homeostasis in rats.

The capacity of aging rats to defend body fluid homeostasis in response to a variety of dipsogenic and natriorexigenic stimuli was assessed. Male and female rats of both the Fischer 344 (FR) and Sprague-Dawley (SD) strains were used and tested at target ages of approximately 5, 10, 15, and 20 mo in both longitudinal and cross-sectional studies. There were no consistent age-related declines in water intake in response to water deprivation or acute administration of hypertonic NaCl; angiotensin (ANG) I, II, III; or isoproterenol. Likewise, there were no major impairments in either urinary excretion of the hypertonic NaCl load or excretion of water or hypotonic NaCl loads, although the latter were excreted more slowly in the older cohorts. The preference/aversion functions for NaCl solutions differed between SD and FR rats, but did not change with age except in male FR rats that lost their aversion to dilute NaCl at 20 mo of age. Intake of hypotonic NaCl solution after acute sodium depletion (furosemide treatment) showed a partial decline with age, and the older rats sustained larger estimated sodium deficits after a 6-h repletion period. A more complete age-related decline was observed in the intake of hypertonic NaCl stimulated by chronic dietary administration of a kininase II inhibitor (ramipril). Male rats of 15-20 mo of age showed no ramipril-induced sodium appetite. Brain ANG II receptor density, determined by autoradiography, declined by almost 50% in the paraventricular nucleus at 20 mo of age and declined slightly in the organum vasculosum laminae terminalis but did not decline in either the supraoptic nucleus or subfornical organ. Thus the major deficits in fluid intake in aging rats are related to salt appetite; the mechanism was not identified definitively.

Losartan inhibition of angiotensin-related drinking and Fos immunoreactivity in hypertensive and hypotensive contexts.

We assessed the ability of acute peripheral administration of the AT-1 receptor antagonist, losartan, to reverse both the water intake and Fos-immunoreactivity (Fos-ir) induced in rats by either peripheral or cerebroventricular (i.c.v.) administration of angiotensin (Ang) II. We compared this with endogenous generation of Ang II during either hypovolemia or hypotension. Relatively low doses of losartan blocked the dipsogenic effect of peripherally administered exogenous Ang II, but a higher dose (20 mg/kg) was needed to block the dipsogenic effect of i.c.v.-administered Ang II. Fos-ir induced by i.c.v. Ang II was attenuated in SFO and SON by 10-20 mg losartan/kg given peripherally, but Fos-ir in the MnPO and PVN was unaffected. These findings suggest that losartan has limited permeability into the brain. We used peripheral losartan to assess the contribution of Ang II to water intake and Fos-ir responses to peripheral injection of either polyethylene glycol (PEG; a colloid that produces non-hypotensive hypovolemia) or isoproterenol (hypotensive agent). Water intakes were unaffected by the higher dose of losartan given s.c. Intraperitoneal injection of EXP 3174, the active metabolite of losartan that may more readily penetrate the blood-brain barrier, inhibited isoproterenol-, but not PEG-induced water intakes. Fos-ir was induced by PEG and isoproterenol in several regions of the brain also activated by Ang II. Fos-ir was greatly attenuated in the SFO by losartan following administration of PEG, but not isoproterenol, and was either unaffected or increased in SON and PVN after either agent. These data suggest that the increased circulating Ang II following PEG or isoproterenol acts at the SFO and is more readily reversible by losartan in normotensive (PEG) than in hypotensive (isoproterenol) states. Non-Ang neural input to the SON and PVN, presumably from baroreceptors, appears to be sufficient to produce strong Fos-ir in these regions, as well as to engage drinking.

The physiology and brain mechanisms of feeding.

This article is designed as an introduction to the major theoretical models in the field of regulation of eating behavior, and a selective review of relevant neurobiological data. We first critically consider the paradigm of homeostasis as it relates to body energy content, and argue that additional theoretical constructs will be needed to account for the complexity of eating behavior in both nonhumans and humans. We then summarize some of the methods available to the neuroscientist in this area, and address some of their limitations. We review treatments and potential mechanisms that increase food intake, including deprivation, antimetabolites, norepinephrine, and several peptides including neuropeptide Y. We next review treatments that decrease food intake, including a variety of humoral, gastrointestinal, and pancreatic factors, as well as examine central pathways of satiety. This includes a discussion of leptin and other potential anorectic agents. We conclude with a discussion of human obesity and anorexias, and prospects for pharmacotherapy of eating disorders. We emphasize throughout that most regions of the human brain probably make some contribution to feeding behavior, and so a focus on any one area of transmitter/hormone is an unrealistic approach both in basic and applied areas.

Diurnal rhythms of paraventricular hypothalamic norepinephrine and food intake in rats.

Extracellular levels of endogenous norepinephrine (NE) within rat paraventricular hypothalamus (PVN) vary across the diurnal cycle, with a peak in NE level noted at the onset of the dark cycle, at which time feeding occurs in a burst. The present experiment further examined the relationship between food intake and extracellular levels of NE within the PVN and within sites located outside of the hypothalamus. Adult male rats were implanted with concentric microdialysis probes aimed at either the PVN or brain sites outside the PVN. Measures of food intake and of extracellular NE were collected every hour over a 24-h period. Rats with PVN probes exhibited two peaks in extracellular NE. The first peak in PVN NE occurred within 1 h before the onset of the dark phase (ZT11) and was significantly correlated (p < 0.02) with a marked burst of feeding during the first hour of the dark phase. In addition, a second NE peak occurred 8 h into the dark phase (ZT19) but was not accompanied by feeding. Rats bearing non-PVN probes did not exhibit alterations in extracellular NE yet did show a pattern of feeding similar to that noted in the PVN rats. These data support the hypothesis that the burst of feeding evident at the onset of dark is related, in part, to an increase in PVN extracellular NE.(ABSTRACT TRUNCATED AT 250 WORDS)

Conditioned taste aversion in rats induced by the alpha 1-adrenoceptor agonist cirazoline.

Recent studies have indicated that alpha 1-adrenoceptor agonists such as phenylpropanolamine (PPA), cirazoline, amidephrine, and SK&F-89748 suppress food intake in rats. These compounds activate alpha 1-adrenoceptors within the paraventricular hypothalamic nucleus (PVN) and may excite efferent fibers that inhibit feeding. Studies of the effects of alpha 1-agonists suggest a specificity for feeding behavior, but no study to date has evaluated whether these agonists may suppress feeding behavior by the induction of malaise. Accordingly, the present experiment examined the ability of systemically administered cirazoline (0.1, 0.2, and 0.4 mg/kg, IP) to induce conditioned taste aversion (CTA) to a saccharin solution. Significant CTA was noted for 0.2 and 0.4 mg/kg cirazoline but not for 0.1 mg/kg cirazoline, compared to a vehicle treatment. The ED50 for cirazoline-induced aversion was computed to be 0.3 mg/kg, which contrasts with an ED50 value of 0.09 mg/kg for the effect of cirazoline on food intake (computed in other studies). More importantly, a 0.1 mg/kg dose of cirazoline, which is slightly greater than that of the ED50 value for suppression of feeding, did not induce significant CTA in the present study. These results suggest that malaise is not a prominent factor in the suppressive activity of cirazoline on food intake and advocate the use of cirazoline as an effective appetite suppressant.

An assessment of the involvement of paraventricular hypothalamic alpha 2-adrenoceptors in phenylpropanolamine anorexia.

Systemic injection of phenylpropanolamine (PPA), an alpha 1-adrenergic receptor agonist with some activity at alpha 2-adrenergic receptors, suppresses food intake in rats. However, only limited information is available as to the effect of intracranial PPA injections on food and water intake. In Experiment 1, microinjection of PPA (80-240 nM) into the hypothalamic paraventricular nucleus (PVN) induced a dose-dependent suppression of feeding (ED50 = 181 nM) but was without significant effect on water intake. Experiment 2 evaluated the effect of systemic PPA on paraventricular hypothalamic norepinephrine (NE) levels. Rats were treated with either vehicle or 20 mg/kg (IP) PPA prior to a 100-min period in which extracellular NE within the PVN was monitored via an indwelling microdialysis probe. Systemic injection of PPA suppressed extracellular NE level within PVN by approximately 70%, an action consistent with stimulation by PPA of a presynaptic alpha 2-adrenergic autoreceptor. Experiment 3 evaluated whether the alpha 2-adrenergic activity of PPA contributes to its feeding-suppressive action. Unlike prior results using the alpha 1-antagonist benoxathian, PVN microinjection of the alpha 2-antagonist rauwolscine in Experiment 3 of the present study failed to block systemically induced PPA anorexia. These results further support the contention that PVN alpha 1-adrenergic receptors suppress feeding and suggest that PPA's alpha 2-adrenergic effects do not modulate the anorexic action of PPA.

Effects of intra-PVN injections of d- and l-norephedrine on feeding in rats.

Phenylpropanolamine (PPA) is thought to inhibit feeding by activation of alpha 1-adrenergic receptors within the paraventricular hypothalamus (PVN). Systemic injections of the PPA component enantiomers, d- and l-norephedrine (NEP), result in differential suppression of feeding (l-NEP more potent than d-NEP). Whether the norephedrine racemates induce differential anorexia subsequent to injection into the PVN is unknown. In the present study, adult male rats received intra-PVN injections of the d- and l-norephedrine enantiomers (0, 80, 160, and 240 nmol). Significantly greater anorexia was obtained for l-NEP relative to d-NEP. These results document a stereospecific effect of the norephedrine enantiomers within the PVN in inhibiting food intake and suggest that the interaction of these enantiomers with PVN alpha 1-adrenoceptors may mediate the similar difference in potency noted for systemic injections of d- and l-norephedrine.

Effects on food and water intake of the alpha 1-adrenoceptor agonists amidephrine and SK&F-89748.

Activation of alpha-1 adrenoceptors, via systemic injection of agonists such as cirazoline and phenylpropanolamine (PPA), reliably suppresses food intake in rats. These effects are thought to result from stimulation of central alpha 1-adrenoceptors within the rat paraventricular hypothalamic nucleus (PVN), based on studies in which direct injections of cirazoline, methoxamine, phenylephrine and PPA into PVN suppress food intake. Because relatively few alpha 1-agonists have been tested to date using the systemic route of exposure, the present study examined the effects of the alpha 1-adrenoceptor agonists amidephrine and SKF-89748 on food and water intake. Adult male rats received systemic injections (IP) of either amidephrine (0.025, 0.05, 0.01 mg/kg) or of SK&F 89748 (0.01, 0.02, and 0.04 mg/kg). Amidephrine markedly suppressed food intake (ED50 = 0.49 mg/kg) and water intake (ED50 = 0.50 mg/kg), while SK&F 89748 marginally suppressed food intake (ED50 = 0.37 mg/kg) and was less potent in suppressing water intake (ED50 = 0.76 mg/kg). These results document that systemic injection of the alpha 1-adrenoceptor agonists amidephrine and SK&F 89748 induces anorexia with amidephrine exerting greater potency than SK&F 89748. These results further support the hypothesis that stimulation of alpha 1-adrenoceptors suppresses food intake.

Modulation of feeding by hypothalamic paraventricular nucleus alpha 1- and alpha 2-adrenergic receptors.

Noradrenergic receptor populations within the paraventricular hypothalamus (PVN) modulate feeding. Satiated rats exhibit enhanced feeding subsequent to activation of alpha 2-adrenergic receptors within the PVN induced by exogenous infusion of either norepinephrine (NE) or clonidine (CLON). The feeding-stimulatory effect of alpha 2-adrenergic agents presumably reflects an inhibitory action on receptors located on medial hypothalamic "satiety" cells. Adrenergic receptors of the alpha 1-subclass have been identified within the PVN which are excitatory and which may function to suppress food intake. Microinjection into rat PVN of various alpha 1-adrenergic agonists including cirazoline, methoxamine, phenylpropanolamine and phenylephrine suppress feeding; an effect that is reversed by pretreatment with alpha 1-adrenergic receptor antagonists. The present review argues that alpha 1- and alpha 2-adrenoceptors within brain and specifically within the PVN are organized in an antagonistic fashion and that the effects of various adrenergic agonists on feeding may reflect the degree to which these agonists act at alpha 1- and alpha 2-adrenoceptors as well the relative balance of these receptors and their activity within the PVN.

Caffeine exposure sensitizes rats to the reinforcing effects of cocaine.

The present study examined the effect of pre-exposure to a moderate dose of caffeine (20 mg kg-1) on the acquisition of self-administration of cocaine (0.125 mg kg-1/infusion or 0.25 mg kg-1/infusion) in the rat. Rats pre-exposed to caffeine acquired self-administration more rapidly. Furthermore, sensitization to cocaine's reinforcing effects was accompanied by an increase in the neurochemical response of the mesolimbic dopamine system to an acute injection of cocaine (10 mg kg-1, i.p.) as measured by in vivo microdialysis. Thus, the data suggest that exposure to caffeine can increase the reinforcing effects of cocaine, possibly via an enhanced response to the mesolimbic dopamine system.