Intrathecal Oxytocin Research Articles

The hemodynamic effects of intrathecal oxytocin in normal dogs

To evaluate the hemodynamic effects produced by intrathecal administration of oxytocin in healthy isoflurane-anesthetized dogs. Prospective single-dose trial. Six healthy purpose-bred adult dogs weighing between 7.3 and 14.5 kg. Dogs were anesthetized with isoflurane and instrumented. Oxytocin at a dosage of 1.6 microg/kg was administered intrathecally at the cisternal space at time 0. Hemodynamic data were recorded immediately before and at 1, 5, 15, 30, and 60 minutes after oxytocin administration. Statistical analysis included an analysis of variance (ANOVA) for repeated measures over time. A P < .05 was considered significant. Baseline values +/- standard error of the mean for heart rate, mean arterial pressure, central venous pressure, cardiac output, systemic vascular resistance, mean pulmonary arterial pressure, pulmonary arterial occlusion pressure, and pulmonary vascular resistance were 101 +/- 11 beats/minute, 76 +/- 7 mm Hg, 4 +/- 4 mm Hg, 1.9 +/- 0.7 L/min, 3834 +/- 2556 dynes x sec/cm5, 14 +/- 3 mm Hg, 4 +/- 2 mm Hg, and 430 +/- 201 dynes x sec/cm5, respectively. Variations from the baseline values were seen in all parameters after intrathecal oxytocin administration, but no statistically significant differences were found. The intrathecal injection of 1.6 microg/kg of oxytocin is associated with minimal hemodynamic effects during isoflurane anesthesia. This study revealed no clinically significant deleterious effects from the intrathecal administration of oxytocin, and investigations into its use as a perioperative analgesic are therefore warranted.

Oxytocin content of the cerebrospinal fluid of dogs and its relationship to pain induced by spinal cord compression.

To determine whether oxytocin exists in the cerebrospinal fluid (CSF) of dogs and whether the amount of oxytocin in the CSF of dogs with neck or back pain caused by spinal cord compression is significantly different than that in the CSF of clinically normal dogs. Prospective controlled study. A total of 15 purpose-bred beagles and 17 client-owned dogs. CSF was collected by needle puncture of the cerebellar medullary cistern after induction of general anesthesia. Oxytocin levels within the samples were determined through radioimmunoassay. Dogs with spinal cord compression had significantly more oxytocin in their CSF than the clinically normal dogs (13.76 +/- 2.0 pg/mL and 3.61 +/- 0.63 pg/mL, respectively; P < .0001). Dogs with chronic signs (>7 days) had significantly more oxytocin in their CSF than dogs with acute signs (<7 days) (21.60 +/- 0.86 pg/mL and 6.80 +/- 0.81 pg/mL, respectively; P < .0001). Both acutely and chronically affected dogs had significantly more oxytocin in their CSF than the controls (P < .005 and P < .0001 respectively). Dogs with neck and back pain caused by spinal cord compression have significantly more oxytocin in their CSF than clinically normal dogs. Dogs with chronic clinical signs have significantly more oxytocin in their CSF than dogs with acute clinical signs. In humans, intrathecal injection of oxytocin is effective in treating low back pain for up to 5 hours. Intrathecal oxytocin may be a logical choice for perioperative analgesia in dogs undergoing myelography because the intrathecal space is accessed for injection of contrast agent.

Oxytocin-induced stimulation and inhibition of bladder activity in normal, conscious rats—Influence of nitric oxide synthase inhibition

The role of the oxytocin-containing projections to the autonomic nuclei of the spinal cord for lower urinary tract function has not been clarified. The hypothesis was tested that oxytocin acts as a mediator of bladder contraction at the spinal cord level. In conscious female rats undergoing continuous cystometry,intrathecaloxytocin (30 ng ≈ 30 pmoles) significantly increased micturition pressure ( P<0.001), and decreased bladder capacity ( P<0.01) and micturition volume ( P<0.01). Residual volume increased ( P<0.05), and so did the amplitude and frequency of non-voiding contractions ( P<0.01). Immediately after administration of oxytocin, the animals showed frequent stretching movements and yawning, and they licked their tails. The effects of oxytocin were dose-dependent; high concentrations (100 ng) were ineffective. Intra-arterial injection of oxytocin (30 ng) near the bladder had no effect. In isolated detrusor strips, oxytocin caused a concentration-dependent contraction; the concentration-response curve was concentration-dependently shifted to the right by the oxytocin antagonist, 1-deamino, 2-D-Tyr(OEt), 4-Thr, 8-Orn-OT. Intrathecal injection of the antagonist (500 ng), had per se no effect on micturition. However, when the antagonist was given intrathecally 4–5 min prior to intrathecal oxytocin (30 ng), the effects of oxytocin were reduced or completely prevented. When given after intrathecal administration of the nitric oxide synthase inhibitor, N ω-nitro- l,-arginine methyl ester, intrathecal oxytocin (30 ng) abolished micturition within 5–7 min; all animals developed overflow incontinence, and paralysis of the hindlimbs. These results suggests that in the rat, oxytocin, released from descending pathways, may act as a modulator of the micturition reflex at the spinal level, and that it may interact with nitric oxide. The physiological implications of the findings remain to be established.

The exercise pressor reflex is attenuated by intrathecal oxytocin

We tested the hypothesis that oxytocin (Oxt) acts in the lumbar spinal cord to attenuate reflex pressor (mean arterial pressure, MAP) and heart rate (HR) responses to static hindlimb contraction (i.e., the exercise pressor reflex). Thus we compared MAP and HR responses to electrically stimulated hindlimb static contraction in the anesthetized cat before and after intrathecal injection of Oxt (30 pmol, n = 3; 300 pmol, n = 6; or 3 nmol, n = 6). The 300-pmol dose was most effective; it attenuated the pressor response to static contraction by 39 +/- 10% but had no effect on HR. In three other cats, contraction-induced increases in MAP and HR were monitored before and after intrathecal injection of 300 pmol of Oxt + 300 nmol of the selective Oxt receptor antagonist [d(CH2)5(1),O-Me-Tyr2,Thr4,Tyr9,Orn8]vasotocin. Pretreatment with the antagonist eliminated the effect of Oxt on MAP. In an additional 10 cats, increases in these same variables in response to static contraction were compared before and after intrathecal injection of the Oxt antagonist (30 nmol, n = 3 or 300 nmol, n = 7) into the lumbar spinal cord (L1-L7). Whereas 30 nmol of the Oxt antagonist had no effect, the 300-nmol dose augmented the contraction-induced pressor and HR responses by 28 +/- 7 and 32 +/- 17%, respectively. These data imply that endogenous Oxt modulates the exercise pressor reflex by its action on Oxt receptors in the lumbar spinal cord that can attenuate sensory nerve transmission from skeletal muscle.

Intrathecal oxytocin facilitates the spinal nociceptive flexor reflex in the rat.

We examined the effects of intrathecal oxytocin over a wide dose range (10 ng to 10 micrograms) on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanaesthetized rats. Oxytocin facilitated the flexor reflex at all doses. The duration, but not magnitude, of facilitation was dose-related. No reflex depression was observed with intrathecal oxytocin at any dose. It is suggested that activation of spinal oxytocin receptors excites the spinal cord and therefore intrathecal oxytocin is unlikely to be an analgesic agent.

Differential motor and blood pressure effects of intrathecal oxytocin and TRH in the rat

While previous reports have immunocytochemically localized oxytocin and TRH in the spinal cord, the functional significance of these peptides is unclear. The present paper examined this issue and tested the effects of these peptides upon intrathecal administration. We found both peptides produced lasting motor and blood pressure changes. Oxytocin elicited prolonged jerks of the hindlimbs and the tail, while TRH produced an increase of hindlimb muscle tone and tail tremor. TRH in larger doses (5, 10 μg) also caused tail erections and whipping. The motor effects of both peptides were dose-dependent. Intrathecal oxytocin (0.75 or 1.5 IU) caused a transient drop in blood pressure followed by a rise, in 4 out of 7 rats. The other 3 only showed a hypertensive effect. In contrast, intrathecal TRH produced a rise in blood pressure in all the animals tested. These findings suggest that both oxytocin and TRH may play a role in the regulation of motor and automatic functioning at the spinal level.