Non-neurological surgery results in a neurochemical stress response.

There is a paucity of studies assessing changes in measures of human neurotransmission during stressful events, such as surgery. Thirty-five patients without any neurological disorders undergoing knee replacements with spinal bupivacaine anaesthesia and propofol sedation had cerebrospinal fluid (CSF) drawn from a spinal catheter before, three hours after and the morning after surgery. The CSF concentrations of the dopamine metabolite homovanillinic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), which are related to the activity of the dopaminergic and serotonergic systems of the brain, increased sharply during surgery and reached 188% and 166% of their initial concentrations on the morning after the intervention (p < 0.0001). The CSF concentrations of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglucol (MHPG) increased modestly (non-significantly) during and after surgery. The HVA/5-HIAA ratios initially increased but returned to the initial level during the night after surgery. We conclude that non-neurological surgery, in this case to the lower limb, is accompanied by a marked central nervous stress response in spite of a spinal blockade.

Association between thyroid hormone levels and monoaminergic neurotransmission during surgery.

BACKGROUND: Human studies assessing thyroid hormone metabolism in relation to brain monoaminergic activity in vivo are scarce. The few studies that do exist suggest significant associations between thyroid function and monoaminergic activity, but the cause-and-effect relationships are far from elucidated. METHODS: We simultaneously collected cerebrospinal fluid (CSF) and serum samples from 35 patients undergoing orthopaedic surgery before, 3h after and the morning after interventions and performed analyses for thyroid hormones and monoamine metabolites. RESULTS: At baseline, the CSF 3-methoxy-4-hydroxyphenylglycol concentrations were significantly correlated to the serum T(3)/T(4) ratio (rho=0.41, p=0.017). During surgery, serum thyroid hormones and the T(3)/T(4) ratio decreased (p<0.0001), while the CSF T(3)/T(4) ratio increased (p=0.0009). There were no correlations between serum and CSF levels of T(3) and T(4) at any of the samplings. Strong correlations were noted between baseline CSF thyroid hormone concentrations and subsequent increases in CSF 5-hydroxyindoleacetic acid (5-HIAA), and homovanillinic acid (HVA), but not vice versa. CONCLUSIONS: Thyroid hormone levels in serum and CSF during stress seem to be distinctly regulated. Baseline thyroid hormone activity may facilitate changes in brain monoaminergic neurotransmission in response to stress.

Cerebrospinal fluid protein reactions during non-neurological surgery.

OBJECTIVE: To study changes in cerebrospinal fluid (CSF) protein markers of blood-CSF barrier integrity and immunological reactions during surgical stress. SUBJECTS AND METHODS: Thirty-five patients without neurological or psychiatric disorders undergoing knee replacements had CSF and serum samples drawn from spinal and arterial catheters before, 3 h after and the morning after surgery. RESULTS: Serum albumin decreased during surgery and CSF albumin decreased during and after surgery, and, as a consequence, the CSF/serum albumin ratio decreased significantly during the study period, especially after the intervention. In contrast, CSF concentrations of beta-2-microglobuline (beta2M) increased significantly during surgery and remained high. The CSF general marker beta-trace protein (betaTP) remained unchanged. CONCLUSIONS: Central nervous system protein reactions to a non-neurological surgical intervention include sharply decreased permeability of albumin into the CSF and signs of intrathecal inflammatory activity.

Opioid peptides in blood and cerebrospinal fluid during acute stress.

The opioid peptides beta-endorphin and [met]enkephalin are present in the peripheral circulation. Plasma beta-endorphin originates from the pituitary gland and its cosecretion with ACTH is stimulated by a variety of noxious stimuli. Although the adrenal medulla contains high concentrations of [met]enkephalin-containing polypeptides which are costored with catecholamines, and although the adrenal gland appears to secrete [met]enkephalin into the adrenal vein, the relative adrenal contribution to plasma [met]enkephalin appears to be negligible. Plasma concentrations of immunoreactive [met]enkephalin may be increased by insulin and by endotoxic shock, but they are not significantly altered by acute haemorrhagic stress nor by surgical stress. Thus blood plasma concentrations of beta-endorphin, but not of [met]enkephalin, are generally increased during acute stress. The physiological significance of endogenous opioids in the circulation is not known. It is unlikely that transient increases in the concentrations of opioid peptides in peripherally circulating blood modulate nociception, since the peptides do not enter ventricular cerebrospinal fluid in detectable amounts under these conditions. Recent evidence has raised the possibility that circulating opioids may be involved in regulating blood glucose and in activating the immune system. It is also possible that circulating beta-endorphin and related polypeptides have non-opioid actions on a variety of peripheral tissues.

Probable extrapituitary source of the immunoreactive prolactin measured in the cerebrospinal fluid of unanesthetized rats by push-pull cannulation of the 3rd ventricle.

The dynamic pattern of the immunoreactive prolactin (PRL) concentrations in the cerebrospinal fluid (CSF) of the 3rd ventricle was explored by push-pull cannulation during either stimulation or blocking of PRL production in the plasma, which itself was sampled by chronic cannulation of the carotid. Some of the results were compared to the PRL concentrations in CSF samples obtained by 3rd-ventricle puncture. Ether stress, which induced a 4- to 6-fold rise in plasma PRL, altered neither the pulsatile circhoral pattern of PRL in the CSF nor the mean level and amplitude of its pulses. However, the sustained intense hyperprolactinemia induced by haloperidol increased the mean PRL level in the CSF and possibly its pulse rate. Surprisingly, hypophysectomy, which suppressed production of PRL in the plasma, did not alter its baseline level or cycling pattern in the CSF. The possibility that tuberal adenohypophysial cells and/or CNS prolactinergic neurons supply the CSF with PRL is discussed.