questions: jstaylor@uvm slide show (fair use images removed): uvm/~jstaylor/TKST

1. Steele Taylorpresents:A Neuro-Endocrine Approach to The Obstetric and Pediatric Applicationsof Tactile-Kinesthetic Stimulation Therapy questions: jstaylor@uvm.edu slide show (fair use images removed): www.uvm.edu/~jstaylor/TKST.ppt notes and citations: www.uvm.edu/~jstaylor/TKST.doc

2. The Touch Research Institute http://www.miami.edu/touch-research/ http://www6.miami.edu/touch-research/research.htm • Research designs explore the following benefits that might be derived from massage: • Alleviation of depression and anxiety • Improved quality of sleep • Pain reduction on neurological and soft-tissue levels • Prevention of premature delivery • Weight gain and cognitive/behavioral advances in premature infants • Improved immune function and reduction of symptoms in auto-immune disorders • Alleviation of eating disorders and dissonant body-perceptions • Reduced anxiety and sense of empowerment in the practitioner or parent • Improved social dynamic between practitioner and recipient (mother-infant, etc.) • Studies that compare massage to general relaxation methods demonstrate that tactile-kinestheticpathways are somehow involved to produce an effect that is beyond that of relaxation • Inadequate elucidation of the physiological underpinnings, yet valuable information such as changes in hormone and neurotransmitter levels in response to massage so that outsiders may produce their own hypotheses and interpretations as to the underlying mechanisms

4. Some Complicating Endocrine Considerations • Receptor Type+Expression+Signal Cascades Determine the Response • Selective Estrogen Receptor Modulation • Cardiovascular Epinephrine Receptors • Duration of the Signal Can Alter Feedback and Response • Estrogen feedback to hypothalamus becomes positive to initiate ovulation • Clearance of steroid hormones • Genomic Versus Non-Genomic Effects • Non-genomic: Open/ close ion channels, activate/deactivate enzymes, perform exocytosis • Genomic: protein synthesis, cellular proliferation, cellular differentiation • Inter-Hormonal Interactions • Glucocorticoid (GC) permissive effects @ epinephrine binding sites • Action of estriol to influence oxytocin receptor expression during parturition • Temporary Endocrine Glands • Fetal-Placental unit: substrates, precursors, active hormones • Levels are difficult to measure because activity is primarily local • Behavioral/Environmental Activators • Stress responses and coping behaviors • Placebo and somatoform phenomena • Endocrine Regulation of Brain/Behavior • Thyroid, Adrenal Cortex, and Gonads profoundly impact brain development and function • Might be considered as peripheral-diffuse-modulatory-systems • Adipose, GI, and other tissues also hormonally regulate behavior

5. Obstetric/Pediatric Complications Treatable with Massage andExplainable via Neuro-Endocrine Principles • Back Pain / general discomfort during pregnancy • Depression/anxiety/stress during and/or after pregnancy • Premature or low birth weight delivery Alex Grey www.alexgrey.com

6. Pain During Pregnancy: • Back pain affects over half of all pregnant women and may significantly impact outlook, mood, daily activities, and sleep • Back Pain: Two Types • Lower Back • Center of gravity moves anteriorly • Loss of abdominal tone→ lumbar lordosis and spasm • Increased pressure on intervertebral discs • Pelvic • Relaxin - induced softening of pelvic ligaments and pubic symphysis to produce pelvic widening • Crucial for successful delivery, not very convenient otherwise • Walking, lifting, rotating can become painful • Referred pain from inferior vena cava • Proper positioning to alleviate pressure

7. Mechanisms of Referred Pain • Visceral and cutaneous nociceptor axons converge on the same interneurons in the spinal cord • Signal becomes mixed and visceral pain is perceived as cutaneous • Important warning sign/diagnostic tool • Angina pectoralis is the classic example • During pregnancy, pressure on the inferior vena cava produces referrals to the pelvic region and lower back • Immediate relief: positioning (left-side-lying) • Long term relief: yoga, chi gung, etc. • Ultimate relief: delivery! http://www.mona.uwi.edu/fpas/courses/physiology/ neurophysiology/ReferredPainMech.gif

8. Pain Regulation in the Spinal Cord:The Gate Theory • Cutaneous nociceptors (pain) and mechanoreceptors (touch, pressure) interact with ‘gating’ interneurons in the dorsal horns • Mechanical stimulation at the site of pain may override/inhibit the projection of a pain signal up the spinothalamic tract • Instinctively rubbing/compressing bruised tissue • Broad gliding, friction, and vibrating massage strokes www.burtonreport.com/images/GateTheory432GIF.gif http://www.nursece.com/onlinecourses/imagesPain/Fig2.gif

9. Pain Regulation in the Brain:The Mother’s Kiss and Placebo Mechanisms http://www.annkullberg.com/Shows/2003/Hild.jpg http://www.sciencemag.org/cgi/content/full/288/5472/1769 • Cross-talk occurs between higher emotional regions, ascending pain-signals, ascending pressure signals, pain-localization regions, pain-anticipatory and avoidance regions, analgesia anticipatory regions (placebo regulators), and pain regulating pathways • Emotional status powerfully influences the degree of pain that is perceived • Sympathetically maintained pain = centrally produced hyperalgesia • Nociceptors become sensitive to and activated by norepinephrine due to prolonged exposure • Periaqueductal gray matter (PAG) of the midbrain, appears to be a critical mechanism in pain regulation, and may be innervated by endorphin producing neurons of the hypothalamus, as well as other regions • Electrical stimulation of the PAG produces remarkable analgesic effects • Top-Down Effect: PAG activates serotonergic cells in the rostral ventral medial nuclei (RVM) of the brainstem, which projects axons down the spinal cord that can effectively stifle pain signals • Distracting tasks are highly effective analgesic tools • Lamaze breathing, visualization, massage, other

10. Pain Regulation at the Soft Tissue Level • Muscle tightness/spasm may compress nerves or obstruct vascular supply • Hypoxia / ischemia triggers pain pathways via vascular signals and irritating waste products from anaerobic muscle metabolism • Inflammation may also occur as a result, causing local hyperalgesia • Massage therapy shuts off spasm/holding patterns on a neurological level • Golgi tendon organs reflexes inhibit muscle contraction • Disruption of holding patterns generated beneath the awareness of the brain • Massage therapy improves local circulation thus alleviating local ischemia • Performed gradually and over a series of treatments to avoid reperfusion injury • Massage, stretching, and strengthening all help to stabilize and maintain normal joint position and function, especially in the lower back and pelvic regions www.amazingbirths.com/images/massage.jpg www.yogaretreats.ie/images/Nataraj2.jpg

11. STRESSOR Uncertainty, lack of control, inadequacy (perceived): labor (acute) motherhood (perpetual) Frustration: inability to perform tasks previously capable of performing Movement, consumption, career, travel, etc. Environmental withdrawal and/or exposure to novel settings Workplace withdrawal, new dwelling, new community, etc. Social withdrawal, low social support, novel social settings Spouse/father, family, friends, colleagues Pain and discomfort COUNTER-STRESSOR Gain mastery of situation Education, planning, birthing classes, strategizing, networking, nesting, etc. Find new rewarding tasks, future oriented versus prisoner of the past Walking, yoga, swimming, etc. Consume flavorful, colorful, and intriguing foods and beverages: Embrace and network in new env. Nesting behavior: prepare dwelling for amazing new occupant Embrace and pursue supportive/ rewarding relationships Fetus, family, spouse, friends with children Go Shopping… Potential Factors Promoting and Alleviating Stress During Pregnancy Psychoendocrinological research cites the following factors as activators and deactivators of stress responses, as determined by GC levels, skin conductance response, sympathoadrenal activity, etc. (many of these stimuli/stressors are non-removable and beyond our scope as health care practitioners…treatment must occur on the level of adaptation and coping)

12. Fetal Consequences of Traditionally Prescribed Anti-Depressant and Anxiolytic Agents • Benefits/risks must be weighed before use during pregnancy • Tricyclic antidepressants, SSRI’s, MAOI’s, benzodiazepenes, etc. • Most are not likely teratogens, yet most are grade C or lower and cross placenta • Neonatal-withdrawal is a common result of fetal exposure • Inconsolable crying, irritability, feeding difficulties, tachycardia, blood sugar abnormalities • May last weeks to months • Tricyclic antidepressants: Grade B-D • Growth Malformations (imipramine, amitriptyline and relatives) • Neonatal Withdrawal • MAOI’s: Grade C • Growth Malformations (tranylcypromine, isocarboxazid) • SSRI’s: Grade B (fluoxetine, sertraline, etc.), C (fluvoxamine) • More research necessary, caution recommended • Benzodiazepenes: Grade D • Neonatal Withdrawal Symptoms • Cleft-Palate and other malformations (diazepam, chlordiazepoxide) • Barbiturates: just don’t • May be necessary if severe epilepsy or severe anxiety prior to labor • Minor congenital defects • Fetal hemorrhage • Neonatal withdrawal

13. General Adaptation Syndrome Model

14. Factors Promoting Excess GC Output • GC’s are a reliable indicator of the degree of stress that is experienced by the organism in environmental settings • Prolonged exposure and/or failure to cope will produce over-stimulation of the hypothalamic-pituitary-adrenal axis • GC’s are lipid soluble and readily diffused across blood-brain-barrier • Widespread receptors in brain account for GC’s ability to influence behavior • Slow clearance from cerebrospinal fluid causes prolonged exposure in brain • Delicate feedback loop increases susceptibility to hypercortisolemia: • Feedback regulation of hypothalamic CRH secretions is heavily dependent on inhibition from the hippocampus, which heavily expresses GC receptors • Ironically, although hippocampal cells rely on GC’s for their development, repeated exposure can cause hippocampal atrophy and apoptosis • Reduced feedback causes out of control GC production and vicious cycle • Hypercortisolemia produces a cascade of physiological impairments and neurological/behavioral alterations as demonstrated on previous slide • Infants born to depressed mothers tend to mimic the maternal biochemical and physiological constitution, including elevated glucocorticoid levels, reduced serotonin and dopamine levels, and behavioral dysfunction

15. Can Stress-Related Maternal Hypercortisolaemia Contribute to the Premature Onset of Parturition? • IF… Stress and depression during pregnancy produce an increased risk for premature delivery, and associated complications • AND… Massage therapy is a highly effective drug-free treatment for the alleviation of stress and depression • THEN… Regular massage during pregnancy can dramatically reduce the occurrence of premature delivery and associated complications • To support this we must establish: • The role of stress hormones in the onset of parturition • The pathways through which massage may alleviate stress hormone activity

16. Endocrinology of Parturition • Considerable evidence suggests that the fetal lungs and brain are responsible for the initiation of labor, and that children continue to control their parents throughout life… • Late in gestation, the fetal adrenal cortex grows considerably, and under the influence of the CRH-ACTH axis, produces large amounts of GC’s and DHEAS • Fetal GC’s stimulate maturation of organs, particularly the lungs • Fetal GC’s stimulate the placenta to increase the conversion of progesterone to estrogens, particularly to estriol or E3 , ( the fetal adrenal supplies 90% of the precursor: DHEAS) • Estriol acts on the uterus to: • Increase the output of prostaglandins, which prime the contractile proteins • Promote the formation of gap junctions within the uterus, which help to effectively coordinate expulsion of the fetus • Promote the expression of oxytocin receptors, which help maintain contractions • Promote collagenase enzymes that ripen the cervix by degrading fibrous connective tissue • Oxytocin, normally antagonized by progesterone, can now operate on uterus • Positive feedback loop is generated as uterine proprioceptors prompt the release of more oxytocin • Fetal protection from maternal glucocorticoids: • Placenta deactivates 85% before they reach fetus • ALL fetal tissue expresses enzymes that deactivate maternal cortisol • (11-hydroxysteroid dehydrogenase) • Fetus maintains high levels of progesterone, which have a stronger binding affinity for GCR’s

17. Preterm Labor Epidemiology • Stress, depression, infection,preeclampsia,fetal/placental hypoxia, diabetes, previous PTL, anemia, hyperthyroidism, smoking, and acute emergency conditions (hemorrhage, etc.) all contribute to PTL • In acute cases, it is contraindicated to prevent PTL • Preventative strategies should be observed by all women, since only 50 % of PTL’s exhibit identifiable risk factors • USA has a higher PTL rate than most industrialized countries • Over 10% of pregnancies, with occurrence still rising • Responsible for 75% of neonatal morbidity and mortality • Neonatal Intensive Care = $5 billion annually • Emotional hardship, economic drain, long-term complications

18. Preterm Labor Onset • Infection (vaginal, uterine, intraamniotic) • May cause up to 30% of preterm deliveries • Cytokines released from leukocytes fighting infection may prompt prostaglandin (PG) release • Bacterial phospholipases may also increase free PG levels • Concurrent reduction in levels of PG dehydrogenase (PGDH), an enzyme that deactivates PG’s and that is normally maintained at high levels during gestation • Glucocorticoids may also reduce the expression of PGDH • Infection may ultimately be linked to general immunosuppression resulting from hypercortisolaemia associated with stress and depression • Preeclampsia and Fetal-Placental Hypoxia • Fetal CRH increases which stimulates increase in placental CRH • Placental CRH operates as a vasodilator • If the attempt to restore blood flow fails, CRH stays high • Fetal adrenal response to CRH-ACTH triggers placenta to initiate labor • Disruption of Feedback Systems From Chronic GC Exposure • Other Adverse Fetal Environments

19. Mechanisms Involved In Physiological Responses to Massage • Tactile - kinesthetic pathways, including oral, apparently interact with the brain and particularly the hypothalamus to: • Diminish stress responses and reduce mobilization of energy reserves • Increase levels of serotonin, dopamine, and norepinephrine • Improve sleep patterns • Shift relative EEG activity from right frontal cortex to left frontal cortex • Activate pain-reduction pathways and reduce pain at its origins • Release growth-hormone releasing hormone (infants) • Strengthen vagal activity • Improved gastric motility • Increased digestive and absorptive hormones such as gastrin and insulin • Reduce heart rate • Anatomical interactions between touch receptors and the hypothalamus via the thalamus and somatosensory cortex are necessary to enable such dramatic physiological alterations

20. Tactile-Kinesthetic Stimulation Benefits via Nonnutritive Suckling, Kangaroo Care and Massage • Nonnutritive Suckling: the first coping mechanism (98% of NICU’s) • Powerful instinct upon birth also occurring in womb as early as 5 months gestation • Analgesic effect reduces fussiness during painful procedures • Improved sleep patterns (REM), growth rates, and shorter hospital stays • Kangaroo Care: tactile, kinesthetic, vestibular, and thermal stimulation (97% of NICU’s) • Improved breastfeeding habits, reduced infections,and shorter hospital stays • Massage Therapy: Dynamic tactile – kinesthetic stimulation (39% of NICU’s) • Deeper pressure is important: light touch may be perceived as aversive • Enhanced growth, social responsiveness, motor behavior, habituation, parental interaction, and shorter hospital stays • (in rats, maternal tongue licking is essential for normal growth and behavior)

21. A Neonatal Massage Sequence Utilized In A TRI Experimental Design • Experimenters treated 40 infants delivered on average 9 weeks preterm and having experienced 3 weeks of intensive care, weighing 2 lbs on average, and free of congenital heart malformations, CNS disturbances, and other anomalies • Performed through portholes of incubator • Procedure: 45 minutes for 10 days at 3 x 15 minute treatments • 5 minutes tactile stimulation • 5 minutes kinesthetic stimulation • 5 minutes tactile stimulation • Tactile stimulation: Prone • From top of head to neck and back x 12 • From neck across shoulders and back x 12 • From upper back to waist and back x 12 • From hips to feet and back on both legs x 12 • From shoulders to the hands and back on both arms x 12 • Kinesthetic treatment: Supine • Flexion / extension (bicycling) to individual arms and legs and then both • Results consistent with benefits listed on previous slide • Infants released from hospital on average 6 days earlier than control group! • Field T, Schanberg SM, ScafidiF et al 1986 Tactile / kinesthetic stimulation effects on preterm infants. Originally published in Pediatrics 77: 654-658, Reproduced in Field T 2000 Touch Therapy. Edinburgh: Churchill Livingston.

22. Resources: • Bear MF, Connors BW & Paradiso MA 2007 Neuroscience: Exploring the Brain. 3rd edition. Philadelphia: Lippincott Wilkins and Williams. • Briggs GG, Freeman RK & Yaffe SJ 1998 Drugs in Pregnancy and Lactation. 5th edition. Baltimore: Williams and Wilkins. • Brush FR & Levine S 1989 Psychoendocrinology. San Diego: Academic Press Inc. • Field T 2000 Touch Therapy. Edinburgh: Churchill Livingston. • Field T 2003 Stimulation of Preterm Infants. Pediatrics in Review. 2003;24:4-11. Hadley ME 2000 Endocrinology. 5th edition. New Jersey: Prentice Hall • Gilbert ES 2007 Manual of High Risk Pregnancy and Delivery. 4th edition. St. Louis: Mosby Elsevier. • Karch AM 2006 Focus on Nursing Pharmacology. 3rd edition. Philadelphia: Lippincott Wilkins and Williams. • McMahon SB & Koltzenburg M 2006 Wall and Melzack’s Textbook of Pain. 5th edition. Elsevier Churchill Livingston. • Tulchinsky D & Little AB 1994 Maternal – Fetal Endocrinology. 2nd edition. Philadelphia: W.B. Saunders Company • Van Praag HM, de Kloet R & van Os J 2004 Stress, the Brain and Depression. Cambridge: Cambridge University Press.