Rapid suppression of bone formation marker in response to sleep restriction and circadian disruption in men.

We describe the time course of bone formation marker (P1NP) decline in men exposed to ~ 3 weeks of sleep restriction with concurrent circadian disruption. P1NP declined within 10 days and remained lower with ongoing exposure. These data suggest even brief exposure to sleep and circadian disruptions may disrupt bone metabolism. INTRODUCTION: A serum bone formation marker (procollagen type 1 N-terminal, P1NP) was lower after ~ 3 weeks of sleep restriction combined with circadian disruption. We now describe the time course of decline. METHODS: The ~ 3-week protocol included two segments: "baseline," ≥ 10-h sleep opportunity/day × 5 days; "forced desynchrony" (FD), recurring 28 h day (circadian disruption) with sleep restriction (~ 5.6-h sleep per 24 h). Fasted plasma P1NP was measured throughout the protocol in nine men (20-59 years old). We tested the hypothesis that PINP would steadily decline across the FD intervention because the magnitude of sleep loss and circadian misalignment accrued as the protocol progressed. A piecewise linear regression model was used to estimate the slope (ß) as ΔP1NP per 24 h with a change point mid-protocol to estimate the initial vs. prolonged effects of FD exposure. RESULTS: Plasma P1NP levels declined significantly within the first 10 days of FD ([Formula: see text] = - 1.33 µg/L per 24 h, p < 0.0001) and remained lower than baseline with prolonged exposure out to 3 weeks ([Formula: see text] = - 0.18 µg/L per 24 h, p = 0.67). As previously reported, levels of a bone resorption marker (C-telopeptide (CTX)) were unchanged. CONCLUSION: Sleep restriction with concurrent circadian disruption induced a relatively rapid decline in P1NP (despite no change in CTX) and levels remained lower with ongoing exposure. These data suggest (1) even brief sleep restriction and circadian disruption can adversely affect bone metabolism, and (2) there is no P1NP recovery with ongoing exposure that, taken together, could lead to lower bone density over time.

24-hour profile of serum sclerostin and its association with bone biomarkers in men.

The osteocyte's role in orchestrating diurnal variations in bone turnover markers (BTMs) is unclear. We identified no rhythm in serum sclerostin (osteocyte protein). These results suggest that serum sclerostin can be measured at any time of day and the osteocyte does not direct the rhythmicity of other BTMs in men. INTRODUCTION: The osteocyte exerts important effects on bone remodeling, but its rhythmicity and effect on the rhythms of other bone cells are not fully characterized. The purpose of this study was to determine if serum sclerostin displays rhythmicity over a 24-h interval, similar to that of other bone biomarkers. METHODS: Serum sclerostin, FGF-23, CTX, and P1NP were measured every 2 h over a 24-h interval in ten healthy men aged 20-65 years. Maximum likelihood estimates of the parameters in a repeated measures model were used to determine if these biomarkers displayed a diurnal, sinusoidal rhythm. RESULTS: No discernible 24-h rhythm was identified for sclerostin (p = 0.99) or P1NP (p = 0.65). CTX rhythmicity was confirmed (p < 0.001), peaking at 05:30 (range 01:30-07:30). FGF-23 levels were also rhythmic (p < 0.001), but time of peak was variable (range 02:30-11:30). The only significant association identified between these four bone biomarkers was for CTX and P1NP mean 24-h metabolite levels (r = 0.65, p = 0.04). CONCLUSIONS: Sclerostin levels do not appear to be rhythmic in men. This suggests that in contrast to CTX, serum sclerostin could be measured at any time of day. The 24-h profiles of FGF-23 suggest that a component of osteocyte function is rhythmic, but its timing is variable. Our results do not support the hypothesis that osteocytes direct the rhythmicity of other bone turnover markers (CTX), at least not via a sclerostin-mediated mechanism.

Constraint is associated with earlier circadian phase and morningness: Confirmation of relationships between personality and circadian phase using a constant routine protocol.

Associations among personality, diurnal preference, and circadian phase were investigated using a constant routine laboratory protocol. One hundred and sixty-eight healthy participants aged 18-30 years (Women n = 68) completed either a 30- or 50-hour constant routine under dim-light conditions (<3 lux), during which circadian phase was measured from core body temperature and melatonin. Prior to laboratory admission, self-report measures of personality and diurnal preference were also obtained. The personality trait of Constraint correlated positively with morning diurnal preference and earlier circadian phase, with circadian phase partially mediating the relationship between Constraint and diurnal preference. No other personality variables correlated with circadian phase. Sex was an important covariate in several of the relationships investigated due to lower levels of Constraint and later CBT phase amongst men and was thus controlled for in all relevant analyses. Findings from this highly controlled study are consistent with previous field research in suggesting that earlier circadian phase is associated with the personality trait of Constraint.

Fibrinolysis for intraventricular hemorrhage: an updated meta-analysis and systematic review of the literature.

BACKGROUND AND PURPOSE: Intraventricular hemorrhage is associated with high mortality and poor functional outcome. The use of intraventricular fibrinolytic (IVF) therapy as an intervention in intraventricular hemorrhage is an evolving therapy with conflicting reports in the literature. The goal of this study is to investigate the impact of IVF on mortality, functional outcome, ventriculitis, shunt dependence, and rehemorrhage. METHODS: During March and April 2014, a systematic literature search was performed identifying 1359 articles. Of these, 24 met inclusion criteria. A random effects meta-analysis was performed using both pooled and subset analysis based on study type. RESULTS: Our meta-analysis demonstrated that IVF reduced mortality in intraventricular hemorrhage by nearly half (relative risk [RR], 0.55; 95% confidence interval [CI], 0.42-0.71; P<0.00001), increased the likelihood of good functional outcome by 66% (RR, 1.66; 95% CI, 1.27-2.19; P=0.0003), and also decreased the rate of shunt dependence (RR, 0.62; 95% CI, 0.42-0.93; P=0.02). IVF was not found to be associated with increased rates of ventriculitis (RR=1.46; 95% CI, 0.77-2.76; P=0.25) or rehemorrhage (RR=1.06; 95% CI, 0.66-1.70; P=0.80). We detected no evidence of publication bias. CONCLUSIONS: Our meta-analysis showed that IVF is safe and could be an effective strategy for the treatment of intraventricular hemorrhage. It may reduce mortality, improve functional outcome, and diminish the need for permanent ventricular shunting, while not increasing the risk of ventriculitis or rehemorrhage.

Neurosurgical checklists: a review.

Morbidity due to avoidable medical errors is a crippling reality intrinsic to health care. In particular, iatrogenic surgical errors lead to significant morbidity, decreased quality of life, and attendant costs. In recent decades there has been an increased focus on health care quality improvement, with a concomitant focus on mitigating avoidable medical errors. The most notable tool developed to this end is the surgical checklist. Checklists have been implemented in various operating rooms internationally, with overwhelmingly positive results. Comparatively, the field of neurosurgery has only minimally addressed the utility of checklists as a health care improvement measure. Literature on the use of checklists in this field has been sparse. Considering the widespread efficacy of this tool in other fields, the authors seek to raise neurosurgical awareness regarding checklists by reviewing the current literature.

Regional magnetic fields as navigational markers for sea turtles.

Young loggerhead sea turtles (Caretta caretta) from eastern Florida undertake a transoceanic migration in which they gradually circle the north Atlantic Ocean before returning to the North American coast. Here we report that hatchling loggerheads, when exposed to magnetic fields replicating those found in three widely separated oceanic regions, responded by swimming in directions that would, in each case, help keep turtles within the currents of the North Atlantic gyre and facilitate movement along the migratory pathway. These results imply that young loggerheads have a guidance system in which regional magnetic fields function as navigational markers and elicit changes in swimming direction at crucial geographic boundaries.

Decreased sensitivity of the circadian system to light in current, but not remitted depression.

BACKGROUND: Misalignment of circadian timing in patients with depression has commonly been reported, but the underlying mechanisms are not known. Individual differences in the sensitivity of the circadian system to light affect how the biological clock synchronizes with the external environment and can lead to misalignment of rhythms. We investigated the sensitivity of the circadian system to light in unmedicated (for >3 months) women with a current or previous diagnosis of major depression, and healthy controls. METHODS: Baseline melatonin levels in dim light (<1 lux) were assessed, followed by melatonin levels in normal indoor lighting of 100 lux in order to determine melatonin suppression. RESULTS: Patients currently experiencing a depressive episode showed significantly lower levels of melatonin suppression to light compared to remitted patients and controls, with large effect sizes. Remitted patients and controls showed similar suppression. LIMITATIONS: The relatively small sample, and lack of long-term, within subject assessments, make it difficult to determine the potential causal role of reduced light sensitivity in the development of circadian disruption. CONCLUSIONS: We conclude that hyposensitivity of the circadian system to light may contribute to circadian misalignment in patients with depression. Interventions that increase sensitivity to light or provide stronger light cues may assist in normalizing circadian clock function.

Evening types demonstrate reduced SSRI treatment efficacy.

Selective serotonin reuptake inhibitors (SSRIs) have a profound effect on the circadian system's response to environmental light, which may impact treatment outcomes for patients depending on their habitual light exposure patterns. Here, we investigated the relationship between time-of-day preference, depressive symptoms and self-reported antidepressant treatment response. Evening types reported having taken a higher number of antidepressant medications in the previous 5 years and lower SSRI efficacy than morning types. While undergoing SSRI treatment, evening types also reported more depressive symptoms and suicidality. It is concluded that time-of-day preference may prove informative in predicting SSRI treatment responses.

The SSRI citalopram increases the sensitivity of the human circadian system to light in an acute dose.

RATIONALE: Disturbances of the circadian system are common in depression. Though they typically subside when depression is treated with antidepressants, the mechanism by which this occurs is unknown. Despite being the most commonly prescribed class of antidepressants, the effect of selective serotonin reuptake inhibitors (SSRIs) on the human circadian clock is not well understood. OBJECTIVE: To examine the effect of the SSRI citalopram (30 mg) on the sensitivity of the human circadian system to light. METHODS: This study used a double-blind, placebo-controlled, within-subjects, crossover design. Participants completed two melatonin suppression assessments in room level light (~ 100 lx), taking either a single dose of citalopram 30 mg or a placebo at the beginning of each light exposure. Melatonin suppression was calculated by comparing placebo and citalopram light exposure conditions to a dim light baseline. RESULTS: A 47% increase in melatonin suppression was observed after administration of an acute dose of citalopram, with all participants showing more suppression after citalopram administration (large effect, d = 1.54). Further, melatonin onset occurred later under normal room light with citalopram compared to placebo. CONCLUSIONS: Increased sensitivity of the circadian system to light could assist in explaining some of the inter-individual variability in antidepressant treatment responses, as it is likely to assist in recovery in some patients, while causing further disruption for others.

Creation of genome-wide protein expression libraries using random activation of gene expression.

Here we report the use of random activation of gene expression (RAGE) to create genome-wide protein expression libraries. RAGE libraries containing only 5 x 10(6) individual clones were found to express every gene tested, including genes that are normally silent in the parent cell line. Furthermore, endogenous genes were activated at similar frequencies and expressed at similar levels within RAGE libraries created from multiple human cell lines, demonstrating that RAGE libraries are inherently normalized. Pools of RAGE clones were used to isolate 19,547 human gene clusters, approximately 53% of which were novel when tested against public databases of expressed sequence tag (EST) and complementary DNA (cDNA). Isolation of individual clones confirmed that the activated endogenous genes can be expressed at high levels to produce biologically active proteins. The properties of RAGE libraries and RAGE expression clones are well suited for a number of biotechnological applications including gene discovery, protein characterization, drug development, and protein manufacturing.

Investigating the relationship between sleep and macronutrient intake in women of childbearing age.

BACKGROUND/OBJECTIVE: Reduced sleep is a strong and independent risk factor for weight gain and obesity. Maternal obesity preconception and throughout gestation can increase the risk of adverse pregnancy outcomes and impact on offspring health in later life. This study investigated the relationship between sleeping behaviour and macronutrient intake in childbearing aged women. SUBJECTS/METHODS: We used cross-sectional data from the Australian Longitudinal Study on Women's Health 1973-78 cohort, aged 31-36 years in 2009 (n=8200). Subjective sleeping behaviour was reported and macronutrient intake was measured using a validated food frequency questionnaire. Latent class analysis (LCA) was used to derive sleeping patterns. Multivariate regression analysis was used to investigate the relationships between sleep and macronutrient intake. RESULTS: LCA identified three sleep patterns: (LC1) average sleep (~8 h) with no adverse sleep-related symptoms (n=3570); (LC2) average sleep (~8 h) with sleeping difficulties and severe tiredness (n=2109); and (LC3) short sleep (~6 h) with sleeping difficulties and severe tiredness (n=915). In fully adjusted models, LC2 was inversely associated with percentage energy as protein (b=-0.24; P=0.01) and the protein-to-carbohydrate ratio (b=-0.01; P<0.05). LC3 was positively associated with percentage of energy as fat (b=0.29; P=0.01), saturated fat (b=0.24; P=<0.001) and monounsaturated fat (b=0.09; P=0.04). CONCLUSIONS: Sleeping behaviour patterns were associated with macronutrient intake in childbearing aged women. Improved sleep patterns, together with diet and physical activity strategies, may make it easier for women to achieve a balanced diet and optimise their weight status in preparation for pregnancy.

Ovariectomy of adult rats leads to increased expression of astrocytic basic fibroblast growth factor in the ventral tegmental area and in dopaminergic projection regions of the entorhinal and prefrontal cortex.

Changes in astrocytic function may underlie the neurochemical and morphological alterations in limbic and cortical areas after estrogen loss in adult females. We assessed whether increased expression of basic fibroblast growth factor (bFGF), an astrocytic response involved in injury-induced neuronal plasticity, occurs after ovariectomy. We examined bFGF immunoreactivity (IR) in ovariectomized rats with oil or estradiol benzoate (5 microgram every 4 d; Experiment 1) and in ovariectomized and intact animals (Experiment 2). In the ventral tegmental area (VTA), bFGF-IR and glial fibrillary acidic protein (GFAP)-IR were greater in ovariectomized animals than in animals with estrogen replacement. bFGF-IR in the VTA was greater in ovariectomized than in intact females. In the dorsal raphe, no differences between groups were found in GFAP-IR or bFGF-IR. In mesolimbic dopaminergic target areas within entorhinal cortex (Ent), prefrontal cortex, and nucleus accumbens, bFGF-IR was higher in Ent of ovariectomized animals 4 weeks after surgery in both experiments, but no differences were seen in nucleus accumbens or in an occipital cortical, control, area in either study. In Experiment 2, small increases in bFGF-IR were seen in the prefrontal cortex after ovariectomy. In the VTA and Ent, changes in bFGF-IR developed gradually, peaking at 4 weeks and waning at 40 weeks. Furthermore, increased dendritic arbor of Ent layer II/III pyramidal cells was found in ovariectomized females with the use of a modified Golgi-Cox staining procedure. These findings suggest that, within specific regions, ovariectomy induces astrocytic responses similar to those observed after injury that may affect neuronal chemistry and morphology.

What is the risk of a shunt malfunction after elective intradural surgery?

OBJECT: Surgery for CSF diversion is the most common procedure performed by pediatric neurosurgeons. The failure rates for shunts remain frustratingly high, resulting in a burden to patients, families, providers, and healthcare systems. The goal of this study was to quantify the risk of a shunt malfunction in patients with an existing shunt who undergo an elective intradural operation. METHODS: All elective intradural surgeries (cranial and spinal) at Le Bonheur Children's Hospital from January 2010 through June 2014 were reviewed to identify those patients who had a functional ventricular shunt at the time of surgery. Patient records were reviewed to collect demographic, surgical, clinical, radiological, and pathologic data, including all details related to any subsequent shunt revision surgery. The primary outcome was all-cause shunt revision (i.e., malfunction or infection) within 90 days of elective intradural surgery. RESULTS: One hundred and fifty elective intradural surgeries were identified in 109 patients during the study period. There were 14 patients (12.8%, 13 male) who experienced 16 shunt malfunctions (10.7%) within 90 days of elective intradural surgery. These 14 patients underwent 13 craniotomies, 2 endoscopic fenestrations for loculated hydrocephalus, and 1 laminectomy for dorsal rhizotomy. Median time to failure was 9 days, with the shunts in half of our patients failing within 5 postoperative days. Those patients with failed shunts were younger (median 4.2 years [range 0.33-26 years] vs median 10 years [range 0.58-34 years]), had a shorter time interval from their previous shunt surgery (median 11 months [range 0-81 months] vs median 20 months [range 0-238 months]), and were more likely to have had intraventricular surgery (80.0% vs. 60.3%). CONCLUSIONS: This is the first study to quantify the risk of a shunt malfunction after elective intradural surgery. The 90-day all-cause shunt failure rate (per procedure) was 10.7%, with half of the failures occurring within the first 5 postoperative days. Possible risk factors for shunt malfunction after elective intradural surgeries are intraventricular surgical approach, shorter time since last shunt-related surgery, and young age.

Chronic continuous or intermittent infusion of cocaine differentially alter the concentration of neurotensin-like immunoreactivity in specific rat brain regions.

Neurotensin (NT) is an endogenous brain tridecapeptide that exhibits selective anatomic and neurochemical interactions with rat brain dopaminergic systems. Because modulation of dopaminergic neurotransmission may underlie many of the behavioral properties of cocaine, the effects of both acute and chronic administration of cocaine on the concentration of NT-like immunoreactivity (NT-LI) in specific brain regions was determined. Adult male rats were treated with cocaine for 14 days at a dose of 40 mg/kg/day (0.118 mmoles/kg/day) administered as either 1 subcutaneous injection per day, or infused continuously using subcutaneously implanted minipumps. Neurotensin-like immunoreactivity in specific brain regions was then measured 24 hours or 8 days following drug administration. After 24 hours of withdrawal from daily subcutaneous injection, the concentration of NT-LI was significantly increased in the substantia nigra (SN) and frontal cortex. After 24 hours of withdrawal from continuous infusion with cocaine, NT-LI was increased only in the SN. After 8 days of withdrawal, NT-LI was increased in the SN of rats treated with daily subcutaneous infections of cocaine, but not in the group treated with continuous infusion. Twenty-four hours following a single acute injection of 40 mg/kg of cocaine, NT-LI was increased in the SN and nucleus accumbens. These results provide evidence consistent with a neuroanatomically selective involvement of NT systems in the behavioral and/or addictive properties of cocaine.

Analysis of receptor/ligand interactions using whole-molecule randomly-mutated ligand libraries.

We report a novel method for the analysis of protein ligands using a whole molecule mutagenesis/phage display system. The cDNA for the inflammatory polypeptide C5a was used as template in a PCR reaction doped with mutagenic nucleoside triphosphates (dP and 8-oxo-2'deoxyguanosine (8-oxodG)) to allow introduction of mutations in a highly controlled manner throughout the cDNA. The resultant library of mutants was displayed on the surface of phage and functional polypeptides were selected by several rounds of selection against the cells bearing the receptor for C5a. Following selection only a limited number of residues in C5a were found to be mutated, suggesting that mutations in key residues involved in the maintenance of structure and in receptor binding had been eliminated. The selected C5a sequences had a higher affinity for receptor than wild type phage-C5a conjugates. As this method for analysing the functional characteristics of proteins does not rely on knowledge a priori of structure, it may be useful for affinity maturation or analysis in a wide range of protein ligand/receptor systems.

Centrally administered neurotensin suppresses locomotor hyperactivity induced by d-amphetamine but not by scopolamine or caffeine.

The effects of intracisternally (i.c.) administered neurotensin (NT) on locomotor responses to scopolamine and caffeine, two psychomotor stimulants which do not depend on an intact mesolimbic dopamine (DA) system, were compared with the effects of the peptide on locomotion induced by d-amphetamine, which does depend on this DA system. Adult rats were injected intracisternally with 30 micrograms of neurotensin or vehicle. Immediately following these injections, the rats received intraperitoneal injections of either d-amphetamine (1, 2 or 3 mg/kg), scopolamine (0.25, 0.5, 1.0 or 2.0 mg/kg), caffeine (5, 15, 30 or 50 mg/kg) or the appropriate vehicle. After a 10 min recovery period, interruptions of photocells by ambulatory and non-ambulatory behavior were recorded every 30 min for 2 hr. Analyses of variance indicate that d-amphetamine and caffeine significantly elevated locomotor and non-locomotor activity at every dose tested. Scopolamine elevated locomotor activity at every dose and non-locomotor activity at 0.5, 1.0 and 2.0 mg/kg. Statistical analysis revealed that neurotensin significantly suppressed the locomotor response to 2 and 3 mg/kg of d-amphetamine but did not suppress the locomotor responses to any dose of scopolamine or caffeine or the non-locomotor responses to any of the three stimulants tested. Behavioral ratings of stereotyped responses indicated that neurotensin altered none of these responses to any stimulant tested. These findings are consistent with previous behavioral and biochemical data which indicate that neurotensin modulates the activity of the mesolimbic, but not nigroneostriatal, DA system and moreover, demonstrate that neurotensin does not simply induce a non-specific impairment of locomotor activity.

Estrous odors and sexually conditioned neutral odors activate separate neural pathways in the male rat.

Olfactory stimuli play important roles in sexual behavior. Previous studies have demonstrated that both estrous odors and initially neutral odors paired with copulation influence the sexual behavior of male rats. The present study examines the pattern of neural activation as revealed by Fos immunoreactivity (Fos-IR) following exposure to bedding scented with either a neutral odor (almond) paired previously with copulation, estrous odors or no odor. Following exposure to estrous odors Fos-IR increased in the accessory olfactory bulb, medial amygdala, medial bed nucleus of the stria terminalis, medial preoptic area, ventromedial hypothalamus, ventral tegmental area, and both the nucleus accumbens core and shell. Conversely, following exposure to the sexually conditioned odor Fos-IR increased in the piriform cortex, basolateral amygdala, nucleus accumbens core, and the anterior portion of the lateral hypothalamic area. In addition, following exposure to almond odor Fos-IR increased in the main olfactory bulb independent of its pairing with copulation. These patterns of Fos-IR following exposure to estrous or sexually conditioned odors were not influenced by either the addition or omission of the other type of odor. These findings demonstrate that estrous and sexually conditioned odors are processed by distinct neural pathways and converge in the nucleus accumbens core, suggesting that this structure has a unique role in processing sexual stimuli of both pheromonal and olfactory natures.

Olfactory stimulation enhances light-induced phase shifts in free-running activity rhythms and Fos expression in the suprachiasmatic nucleus.

There is evidence to suggest that the olfactory and circadian systems are linked, functionally, and that olfactory stimuli can modulate circadian rhythms in mammals. Furthermore, olfactory bulb removal can alter free-running rhythms in animals housed in constant darkness and can attenuate the effect of social stimuli on photic entrainment of circadian rhythms. The mechanisms through which olfactory stimuli influence circadian rhythms are not known. One possibility is that olfactory stimuli influence circadian rhythms by modulating the activity of the circadian clock located in the hypothalamic suprachiasmatic nucleus. To study this, we assessed the effect of olfactory stimulation on free-running rhythms and on photic resetting of the circadian clock in rats using phase shifts in wheel-running rhythms and expression of the transcription factor Fos in the suprachiasmatic nucleus. We found that brief exposure to an olfactory stimulus, cedar wood essence, in the subjective day or subjective night had no effect on either free-running rhythms or Fos expression in the suprachiasmatic nucleus, but that when presented in combination with light, the odor dramatically enhanced light-induced phase shifts and Fos expression in the suprachiasmatic nucleus. Olfactory stimulation alone induced Fos expression in several structures that innervate the suprachiasmatic nucleus, pointing to ways by which stimulus information transmitted in the olfactory pathways could gain access to the suprachiasmatic nucleus to modulate photic resetting. These findings, showing that clock resetting by light can be facilitated by olfactory stimulation, point to a mechanism by which olfactory cues can modulate entrainment of circadian rhythms.

Predominant presence of beta-arrestin-1 in small sensory neurons of rat dorsal root ganglia.

Reverse transcription-polymerase chain reaction and western immunoblot analyses were performed to demonstrate the presence of beta-arrestin-1 in rat dorsal root ganglion. beta-Arrestin-1 existed as two alternatively spliced variants, although predominantly in its untruncated form. Several factors affected the visualization of the truncated version on a sodium dodecyl sulfate-polyacrylamide gel; however, the isoform was clearly detected on a two-dimensional gel. We further localized beta-arrestin-1 immunoreactivity in the sensory neurons of the 5th lumbar dorsal root ganglia. Beta-arrestin-1-immunoreactive neurons accounted for approximately 60% of the sensory neurons, and approximately 88% of the beta-Arrestin-1 immunoreactive neurons fell into a category of small neurons having a diameter of 10-30 microm. Members of the arrestin superfamily play crucial roles in the desensitization of G protein-coupled receptors. Our data demonstrating the presence of beta-arrestin-1 in the rat dorsal root ganglion at both messenger RNA and protein levels support the idea that beta-arrestin- participates in receptor desensitization in the sensory neurons. Furthermore, because small-size neurons of dorsal root ganglion are often implicated in nociception, the predominant presence of beta-arrestin-1 immunoreactivity in small-size sensory neurons suggests that beta-arrestin-1 may have a role modulating nociceptive signals.