Evidence Based Medicine: Neuromodulation And Kidney Disease


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If, as gerontologists insist, “Age is not a disease,” then why does getting old seem so hard for some?1

True, declaring that an animal companion’s declining organ function and pain are “just a result of getting old and there’s nothing we can do about it” is unacceptable.

Furthermore, a hands-off approach may unjustly limit a caregiver’s options. Many human parents of dogs and cats want to do more; they need direction and information from their veterinarians about what to pursue and when.

Accumulating evidence reveals that over time, the autonomic nervous system weakens in its ability to respond appropriately to endogenous and exogenous provocation. This may invoke a persistent state of vasomotor and glandular dysregulation that ultimately culminates in organ disrepair.2

However, certain natural, drug-free methods help offset age-related derangements in metabolic and musculoskeletal capacity. Termed “somatic afferent stimulation,” techniques such as acupuncture, massage and laser therapy aid autonomic function and circulatory health.

Specifically, they bolster the endogenous capacity of the nervous system to autocorrect autonomic control of organ function.3 This translates into a host of potentially effective integrative medicine options for geriatric veterinary patients currently facing numerous end-of-life challenges, such as renal impairment, cardiovascular crises and cognitive decline.

Acupuncture

Now that veterinarians have the opportunity to learn medical acupuncture, they also understand that acupuncture works through neuromodulation and not fairy-tale pseudoscience.

This allows them to better understand how somatic afferent stimulation affects their patients. For autonomic regulation alone, evidence exists for acupuncture neuromodulation as an adjunctive approach for insulin resistance, hypertension, endocrine abnormalities4, cerebral hemodynamics5, gut motility and secretion6, cardiovascular regulation7 and much more.

Renal impairment, in particular, commonly plagues aging veterinary patients. Many veterinary acupuncturists claim benefits for these patients in terms of quality of life, appetite, activity levels and even in blood urea nitrogen and creatinine levels. What is the mechanistic basis for this and is there any evidential support?

Mechanistically, medical acupuncture affects the central, peripheral and homeostatic nervous systems. In order to augment the ability of the autonomic nervous system to respond to states of imbalance related to renal function, somatic afferent stimulation from acupuncture has to reach key sites in the brain that restore homeostasis. For the kidney, this pertains at least in part to affecting blood pressure, ureteral motility and vascular tone to the organ.

Specifically, spinal segmental influences evoked by needling points in the thoracolumbar and lumbar regions activate spinal nerve branches that encourage modulation of spinal cord function.

As signals reach the spinal cord, regulation and modification of autonomic activity and pain take place. Neural crosstalk between somatic and visceral functions occurs via connecting interneurons.8 By reducing sensitization and heightened sympathetic tone stemming from lumbar spinal cord segments that oversee renal circulation, acupuncture on the body wall can affect kidney function through somatosympathetic nervous system connections.

Afferent fibers from acupuncture sites on the pelvic limb participate in somatosympathetic reflex avenues that affect parasympathetic (vagal) pathways.9 That is, input from the fibular nerve enters the spinal cord and ascends to the brainstem at a somatoautonomic convergence site known as the nucleus tractus solitarius. Secondary influences on the limbic system, hypothalamus and cortex further the neuromodulatory impact on autonomic activity and the perception of pain.

While studies documenting the effects of acupuncture on veterinary patients with kidney disease are practically non-existent, the human and experimental animal literature contains several promising papers that may provide insight into the mechanisms and possible outcomes of these techniques as extrapolated to clinical animals such as dogs, cats and rabbits.

Hemodialysis

One area of study involves symptom management for patients receiving hemodialysis.

The anti-inflammatory and opioidergic benefits of acupuncture may serve as some of the mechanisms by which acupuncture improves quality of life in these patients.

Chronic inflammation in dialysis patients may play a role in their fatigue, depression, sleep disturbances and lower survival rates.10 Endogenous opioid release via acupuncture can reduce the pain and uremic pruritus associated with end-stage renal disease.

An uncontrolled, prospective, observational pilot study reported on the effects of acupuncture for patients on hemodialysis. They reported improved emotional well-being and less fatigue as well as significant changes in measures related specifically to their kidney disease. Far infrared ray stimulation of acupuncture points also decreased stress and fatigue and influenced ANS activity as assessed by heart rate variability analysis.11 About 13 percent of humans with ESRD who receive hemodialysis frequently suffer from the aforementioned uremic pruritus, otherwise known as renal itch. This incompletely understood problem responds poorly to conventional approaches. However, a randomized, controlled clinical trial published in Nephrology Dialysis Transplantation reported benefits from stimulation of an acupuncture point at the elbow (Large Intestine 11, or LI 11) in comparison to another more proximal position on the brachium.12 For kidney health itself, researchers studied the effects of electroacupuncture on a point near the medial malleolus (Kidney 3, or KI 3) in terms of its effects on two proteins, NAD-dependent isocitrate dehydrogenase and quinone reductase.

NAD-dependent isocitrate dehydrogenase occurs in the mitochondrion and is the important rate-limiting enzyme in the tricarboxylic acid cycle. Its link to ATP production, energy metabolism and repair processes indicates a possible role in kidney function and protection from nephron stress, according to the authors.13 Quinone reductase protects the body from oxidative and electrophilic stress and confers anti-inflammatory benefits for the kidney.

Levels of both NAD-dependent isocitrate dehydrogenase and quinone reductase showed a three-fold rise in the kidney of rats that received electroacupuncture at KI 3. The authors claim that this suggests a potential value in improving kidney function, energy metabolism and cellular defense while also fighting inflammation.

More To Do

While more remains to be understood regarding when and how to begin neuromodulatory protocols in aging patients and in those with renal disease, it is clear through mechanistic research on acupuncture that improving autonomic tone and function is possible.

As Hotta and Uchida commented, “We are just beginning to define the changes in autonomic nervous system structure and function that occur with aging, a critical first step toward a deeper understanding of the underlying pathophysiology and the sequence of system changes and responses. The basic question of what is actually the result of aging, an increased sympathetic (or parasympathetic) tone or a decreased responsiveness to sympathetic (or parasympathetic) activity, will be challenging to resolve because the two are so thoroughly intertwined. … Declines in the autonomic nervous regulatory functions can significantly impair the quality of life of elderly patients.”

Fortunately for veterinarians, we have, literally at our fingertips, a benign and relatively non-invasive mechanism by which to support ANS function; i.e., acupuncture. The time to submit it to further study with hypothesis-driven research in veterinary patients is now. 

Dr. Robinson, Dipl. ABMA, FAAMA, oversees complementary veterinary education at Colorado State University.

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FOOTNOTES

1. Skelton D. Age is not a disease.  Can Fam Physician. 1979;25:353-357.

2. Hotta H and Uchida S. Aging of the autonomic nervous system and possible improvements in autonomic activity using somatic afferent stimulation. Geriatr Gerontol Int. 2010;10(Suppl 1):S127-S136.

3. Hotta H and Uchida S. Aging of the autonomic nervous system and possible improvements in autonomic activity using somatic afferent stimulation. Geriatr Gerontol Int. 2010;10(Suppl 1):S127-S136.

4. Liang F and Koya D. Acupuncture: is it effective for treatment of insulin resistance? Diabetes, Obesity and Metabolism. 2010;12:555-569.

5. Hori E, Takamoto K, Urakawa S, et al. Effects of acupuncture on the brain hemodynamics. Autonomic Neuroscience: Basic and Clinical. 2010;157:74-80.

6. Noguchi E. Acupuncture regulates gut motility and secretion via nerve reflexes. Autonomic Neuroscience: Basic and Clinical.  2010;156:15-18.

7. Li P, Tjen-A-Looi SC, and Longhurst JC. Nucleus raphe pallidus participates in midbrain-medullary cardiovascular sympathoinhibition during electroacupuncture. Am J Physiol Regul Integr Comp Physiol. 2010;299:R1369-1376.

8. Manni L, Rocco ML, Paparo SB, et al. Electroacupuncture and nerve growth factor: potential clinical applications. Archives Italiennes de Biologie. 2011;149:247-255.

9. Ohsawa H, Okada K, Nishijo K, et al. Neural mechanism of depressor responses of arterial pressure elicited by acupuncture-like stimulation to a hindlimb in anesthetized rats. Journal of the Autonomic Nervous System. 1995; 51: 27-35.

10. Kim KH, Kim T-H, Kang JW, et al. Acupuncture for symptom management in hemodialysis patients: a prospective, observational pilot study. J Alt Comp Med. 2011; 17(8):1-8.

11. Su L-H, Wu K-D, Lee L-S, et al. Effects of far infrared acupoint stimulation on autonomic activity and quality of life in hemodialysis patients. Am J Chin Med. 2009;37(2):215-226.

12. Chou C-Y, Cheng YW, Kao M-T, et al. Acupuncture in haemodialysis patients at the Quchi (LI 11) acupoint for refractory uraemic pruritus. Nephrol Dial Transplant. 2005;20:1912-1915.

13. Li C-R, Cheng Z-D, Zhang Z-X et al. Effects of acupuncture at Taixi acupoint (KI 3) on kidney proteome.  Am J Chin Med. 2011;39(4):687-692.

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