***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: Hypersensitivity to a variety of sensory stimuli is a feature of persistent whiplash associated disorders ( WAD ) . However , little is known about sensory disturbances from the time of injury until transition to either recovery or symptom persistence . Quantitative sensory testing  ( pressure and thermal pain thresholds , the brachial plexus provocation test ) , the  sympathetic vasoconstrictor reflex and psychological distress ( GHQ‐28 ) were prospect ively measured in 76 whiplash subjects within 1 month of injury and then 2 , 3 and 6 months post‐injury . Subjects were classified at 6 months post‐injury using scores on the Neck Disability Index : recovered ( < 8 ) , mild pain and disability ( 10–28 ) or moderate/severe pain and disability ( > 30 ) . Sensory and sympathetic nervous system tests were also measured in 20 control subjects . All whiplash groups demonstrated local mechanical hyperalgesia in the cervical spine at 1 month post‐injury . This hyperalgesia persisted in those with moderate/severe symptoms at 6 months but resolved by 2 months in those who had recovered or reported persistent mild symptoms . Only those with persistent moderate/severe symptoms at 6 months demonstrated generalised hypersensitivity to all sensory tests . These changes occurred within 1 month of injury and remained unchanged throughout the study period . Whilst no significant group differences were evident for the sympathetic vasoconstrictor response , the moderate/severe group showed a tendency for diminished sympathetic reactivity . GHQ‐28 scores of the moderate/severe group were higher than those of the other two groups . The differences in GHQ‐28 did not impact on any of the sensory measures . These findings suggest that those with persistent moderate/severe symptoms at 6 months display , soon after injury , generalised hypersensitivity suggestive of changes in central pain processing mechanisms . This phenomenon did not occur in those who recover or those with persistent mild symptoms A novel therapy for rheumatoid arthritis , regional sympathetic blockade using guanethidine , was investigated in 24 patients with active disease . In a r and omized double blind short-term ( 14 days ) study , we evaluated the effect of therapy on subjective responses , change in pain , stiffness , and morning stiffness and no objective responses , change in pinch strength , grip strength , and joint tenderness . Compared to placebo , guanethidine produced a decrease in pain ( p less than 0.025 ) and an increase in pinch strength ( less than 0.025 ) over the 2-week duration of the study . The therapeutic effect of guanethidine may be mediated by an interruption of the proinflammatory effects of the sympathetic nervous system OBJECTIVE An earlier pilot study suggested that the late whiplash syndrome is uncommon in Greece . The purpose of the present study is to extend the evaluation to a larger sample , and include the prevalence of specific symptoms in the evaluation . METHODS In a prospect i ve , cohort study , a total of 180 accident victims were consecutively recruited following Emergency ward presentation .  A st and ard question naire asked about neck pain , headache , shoulder pain , limb numbness or pain , and dizziness . Accident victims were followed for 6 months . RESULTS In the initial 4 weeks after the accident , accident victims reported neck pain , headache , shoulder pain , arm numbness or pain , and dizziness , but at 4 weeks more than 90 % had recovered from these , the remainder of the subjects having minor symptoms ( not requiring therapy ) , and returning to their pre-accident state of health ( which included minor symptoms ) . There were no cases of chronic disability . CONCLUSION In Greece , symptoms after an acute whiplash injury are self-limiting , brief , and do not appear to evolve into the so-called late whiplash syndrome Objectives To determine if genetic variation in genes in the hypothalamic – pituitary – adrenal ( HPA ) axis , the primary stress response system , influences susceptibility to developing musculoskeletal pain . Methods Pain and comorbidity data was collected at three time points in a prospect i ve population -based cohort study . Pairwise tagging single nucleotide polymorphisms ( SNPs ) were selected and genotyped for seven genes . Genetic association analysis was carried out using zero-inflated negative binomial regression to test for association between SNPs and the maximum number of pain sites across the three time points in participants reporting pain , reported as proportional changes with 95 % CIs . SNPs were also tested for association with chronic widespread pain ( CWP ) using logistic regression reporting odds ratios and 95 % CI . Results A total of 75 SNPs were successfully genotyped in 994 participants including 164 cases with persistent CWP and 172 pain-free controls . Multiple SNPs in SERPINA6 were associated with the maximum number of pain sites ; for example , each copy of the T allele of rs941601 was associated with having 16 % ( proportional change=1.16 , 95 % CI 1.04 to 1.28 , p=0.006 ) more pain sites compared to participants with the CC genotype . SERPINA6 gene SNPs were also associated with CWP . Significant associations between the maximum number of pain sites and SNPs in the CRHBP and POMC genes were also observed and a SNP in MC2R was also associated with CWP . Associations between SNPs and comorbidity of poor sleep quality and depression explained some of the associations observed . Conclusions Genetic variation in HPA axis genes was associated with musculoskeletal pain ; however , some of the associations were explained by comorbidities . Replication of these findings is required in independent cohorts & NA ; Patients with postoperative ongoing sciatic pain have been shown to exhibit reduced cortisol levels along with enhanced IL‐6 levels . The aim of the present study was to clarify the relationship between a reduced cortisol secretion and enhanced cytokine levels by performing a prospect i ve study on patients with disc herniation . Twenty‐two patients were examined before and after their disc surgery . Twelve healthy , pain‐free subjects matched for age , education and gender constituted the control group . The preoperative examinations included the assessment of the diurnal pattern of cortisol secretion and the feedback sensitivity of the hypothalamus – pituitary – adrenal ( HPA ) axis .  Patients ' subjective stress levels  also were assessed during the preoperative examination . The diurnal pattern of cortisol secretion was again assessed during the postoperative examination . Furthermore , blood sample s were collected to measure catecholamine , adrenocorticotropic hormone (ACTH)‐ and interleukin‐6 ( IL‐6 ) levels before and after measuring the pressure pain thresholds ( PPTs ) . An assessment of the sensitivity of circulating monocytes to the immunosuppressive effects of glucocorticoids was further included in the postoperative examinations .  Failed back  syndrome ( FBS ) patients ( n=12 ) showed a reduced cortisol secretion in the morning hours and enhanced feedback sensitivity of the HPA axis . Furthermore , FBS patients displayed an increased in‐vitro production of proinflammatory cytokines and a relative glucocorticoid resistance of pro‐inflammatory cytokine producing monocytes as compared to non‐FBS patients ( n=10 ) and controls . After PPT measurement FBS patients exhibited an increased norepinephrine but decreased epinephrine response , together with lower ACTH levels and a four times higher plasma IL‐6 response . These findings suggest that chronically stressed patients are at a higher risk for a poor surgical outcome as their reduced cortisol secretion promotes the postoperative ongoing synthesis of proinflammatory cytokines Study Design . An experimental study of motor and sensory function and psychological distress in subjects with acute whiplash injury . Objectives . To characterize acute whiplash injury in terms of motor and sensory systems dysfunction and psychological distress and to compare subjects with higher and lesser levels of pain and disability . Summary of Background Data . Motor system dysfunction , sensory hypersensitivity , and psychological distress are present in chronic whiplash associated disorders ( WAD ) , but little is known of such factors in the acute stage of injury . As higher levels of pain and disability in acute WAD are accepted as signs of poor outcome , further characterization of this group from those with lesser symptoms is important . Material s and Methods .  Motor function ( cervical range of movement [ ROM ] , joint position error [ JPE ] ; activity of the superficial neck flexors [ EMG ] during a test of cranio-cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds , and responses to the brachial plexus provocation test ) , and psychological distress ( GHQ-28 , TAMPA , IES ) were measured in 80 whiplash subjects ( WAD II or III ) within 1 month of injury , as were 20 control subjects . Results . Three subgroups were identified in the cohort using cluster analysis based on the Neck Disability Index : those with mild , moderate , or severe pain and disability . All whiplash groups demonstrated decreased ROM and increased EMG compared with the controls ( all P < 0.01 ) . Only the moderate and severe groups demonstrated greater JPE and generalized hypersensitivity to all sensory tests ( all P < 0.01 ) . The three whiplash subgroups demonstrated evidence of psychological distress , although this was greater in the moderate and severe groups . Measures of psychological distress did not impact on between group differences in motor or sensory tests . Conclusions . Acute whiplash subjects with higher levels of pain and disability were distinguished by sensory hypersensitivity to a variety of stimuli , suggestive of central nervous system sensitization occurring soon after injury . These responses occurred independently of psychological distress . These findings may be important for the differential diagnosis of acute whiplash injury and could be one reason why those with higher initial pain and disability demonstrate a poorer outcome BACKGROUND Perioperative myocardial ischemia is the single most important potentially reversible risk factor for mortality and cardiovascular complications after noncardiac surgery . Although more than 1 million patients have such complications annually , there is no effective preventive therapy . METHODS We performed a r and omized , double-blind , placebo-controlled trial to compare the effect of atenolol with that of a placebo on overall survival and cardiovascular morbidity in patients with or at risk for coronary artery disease who were undergoing noncardiac surgery .  Atenolol was given intravenously before and immediately after surgery and orally thereafter for the duration of hospitalization . Patients were followed over the subsequent two years . RESULTS A total of 200 patients were enrolled . Ninety-nine were assigned to the atenolol group , and 101 to the placebo group . One hundred ninety-four patients survived to be discharged from the hospital , and 192 of these were followed for two years . Overall mortality after discharge from the hospital was significantly lower among the atenolol-treated patients than among those who were given placebo over the six months following hospital discharge ( 0 vs. 8 percent , P<0.001 ) , over the first year ( 3 percent vs. 14 percent , P=0.005 ) , and over two years ( 10 percent vs. 21 percent , P=0.019 ) . The principal effect was a reduction in deaths from cardiac causes during the first six to eight months . Combined cardiovascular outcomes were similarly reduced among the atenolol-treated patients ; event-free survival throughout the two-year study period was 68 percent in the placebo group and 83 percent in the atenolol group ( P=0.008 ) . CONCLUSIONS In patients who have or are at risk for coronary artery disease who must undergo noncardiac surgery , treatment with atenolol during hospitalization can reduce mortality and the incidence of cardiovascular complications for as long as two years after surgery OBJECTIVE Abnormalities of the biological stress response ( hypothalamic-pituitary-adrenal axis and the autonomic nervous system ) have been identified in both fibromyalgia ( FM ) and chronic fatigue syndrome ( CFS ) . Although these changes have been considered to be partly responsible for symptom expression , we examine an alternative hypothesis that these HPA and autonomic changes can be found in subsets of healthy individuals in the general population who may be at risk of developing these conditions . Exposure to " stressors " ( e.g. , infections , trauma , etc . ) may lead to symptom expression ( pain , fatigue , and other somatic symptoms ) in part by precipitating lifestyle changes . In particular , we focus on the effect of deprivation of routine aerobic exercise on the development of somatic symptoms . METHODS Eighteen regularly exercising ( > /=4 h/week ) asymptomatic , healthy adults refrained from physical activity for 1 week . We predicted that a subset of these individuals would develop symptoms of FM/CFS with exercise deprivation , and this manuscript focuses on the baseline HPA axis , immune , and autonomic function measures that may predict the development of symptoms . RESULTS Eight of the subjects reported a 10 % increase in one or more symptoms ( pain , fatigue , mood ) after 1 week of exercise deprivation . These symptomatic subjects had lower HPA axis ( baseline cortisol prior to VO2max testing ) , immune ( NK cell responsiveness to venipuncture ) , and autonomic function ( measured by heart rate variability ) at baseline ( prior to cessation of exercise ) when compared to the subjects who did not develop symptoms . CONCLUSIONS A subset of subjects developed symptoms of pain , fatigue , or mood changes after exercise deprivation . This cohort was different from the individuals who did not develop symptoms in baseline measures of HPA axis , immune , and autonomic function . We speculate that a subset of healthy individuals who have hypoactive function of the biological stress response systems unknowingly exercise regularly to augment the function of these systems and thus suppress symptoms 
    Output:
    
Such pain vulnerability because of stress system function may interact with the effects of biomechanical injury and psychobehavioral responses to influence the development of WAD .