Hurt me! The potential benefit of experiencing periodic pain for health.

Hurt me! The potential benefit of experiencing periodic pain for health.

Background information - this was originally written to be posted to the Calorie Restriction Society listserv. The CR Society practices calorie restriction for health and longevity. See http://www.calorierestriction.org/ for their web site. I've decided to post this to my blog instead of the CR listserv for various reasons I won't go into.

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Substance P (SP) is a chemical used by our nerves to communicate pain. It is located both in peripheral nerves and in the central nervous system. When SP is released our bodies and brain respond by producing protective agents against the SP. These agents include somatostatin (1) and beta-endorphins (natural narcotics). (1) indicates that somatostatin down regulated autoimmune disorders. (2) shows that beta-endorphins are lowered in autoimmune disorders.

In addition to these indirect effects SP has direct effects to down regulate autoimmune disorders. (3) shows SP has long lasting benefits in the treatment of autoimmune modulated diabetes. (4, 5) are also suggestive that substance P might be useful in limiting autoimmune disease.

Continuous exposure to high levels of substance P would not be pleasant. Constant pain is not much of a trade off for limiting the autoimmune diseases common with aging, for example. But what about intermittent pain? My belief is it might be quite beneficial. And particularly so if it is voluntarily received as in competitive athletics or various sexual activities I hope I don't have to explain to you.

Interestingly, cultures going back to the dawn of humanity have had mystic healers called by various names, Shamans being the common name today. These individuals were often what we would call gay or transgendered today. They are probably the first to discover the value of periodic pain for health. (6) explains more.

In a small world isn't it sort of way our founder Roy Walford may have known of some of this. (7) discusses his relationship with his performance artist girlfriend, Barbara T. Smith, at the time he was in Biosphere 2. Barbara appeared to have quite an interest in shamanism. Incidentally if you're new to our group you might think the founding inspiration of CR, Roy Walford would have been quite the stiff prude. After all isn't CR about "restriction?" Ah - but read it again. That is "CALORIE restriction." Not life restriction. (8) is his obituary which shows he really knew how to enjoy life and made doing so a priority. Also note that one of the last things he worked on was the role of immune system malfunctioning in aging.

1. Eur Cytokine Netw. 2000 Jun;11(2):161-76
Somatostatin and somatostatin receptors in the immune system: a review.
ten Bokum AM, Hofland LJ, van Hagen PM.
Department of Immunology, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Communication and reciprocal regulation between the nervous, endocrine and immune systems are essential for the stability of the organism. Among others, cytokines, hormones and neuropeptides have been identified as signalling molecules mediating the communication between the three systems. This review focuses on the role of the neuropeptide somatostatin as an intersystem signalling molecule, with emphasis on the immune system. Somatostatin down-modulates a number of immune functions, among others lymphocyte proliferation, immunoglobulin production and the release of proinflammatory cytokines such as IFN-g. Systemic or local treatment with somatostatin or somatostatin analogues has been shown to be beneficial in a number of in vivo models of autoimmune disease and chronic inflammation. In many of these models somatostatin appears to antagonise the effects of another neuropeptide, substance P. A somatostatin-substance P immunoregulatory circuit has been proposed to operate within murine Schistosoma mansoni-induced granulomas. In this review we extend the model of the somatostatin-substance P immunoregulatory circuit to include data derived from other biological systems, and those relying on human clinical situations. In addition, we present a hypothesis on the regulation of the default class of immune response within a tissue, based on the local balance of pro-and anti-inflammatory neuropeptides.
PMID: 10903795

2. J Neuroimmunol. 1999 Jun 1;97(1-2):129-33
Hypothalamic beta-endorphin concentrations are decreased in animals models of autoimmune disease.
Sacerdote P, Lechner O, Sidman C, Wick G, Panerai AE.
Department of Pharmacology, University of Milano, Milan, Italy. paola.sacerdote@unimi.it
Complex interactions between the neuroendocrine and the immune systems are present in autoimmune diseases. The central opioid peptide beta-endorphin (BE) has been shown to modulate peripheral immune responses in normal animals. In the present study we analyze the hypothalamic concentrations of this peptide in two models of spontaneous autoimmune disease, the MRL [corrected] lpr/lpr mouse, that develops a lupus-like autoimmune disease, and the obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis. In both instances, hypothalamic concentrations of BE are significantly lower than normal controls. In MRL [corrected] lpr/lpr mice, BE is already lower at 1 month of age, when no clinical sign of the disease is yet present. Similarly, low levels of BE are observed in OS chickens before the onset of thyroiditis, i.e., already at the embryonic stage. Moreover, a further decrease of BE is observed in OS chickens in correspondence with the first signs of thyroid mononuclear infiltration. Considering the immunosuppressive effects exerted by central BE, these results are suggestive of the fact that in autoimmune disease prone animals the low hypothalamic concentrations may be one of several factors predisposing for the development of autoimmune disease.
PMID: 10408966

3. Cell. 2006 Dec 15;127(6):1123-35
TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes.
Razavi R, Chan Y, Afifiyan FN, Liu XJ, Wan X, Yantha J, Tsui H, Tang L, Tsai S, Santamaria P, Driver JP, Serreze D, Salter MW, Dosch HM.
Neurosciences and Mental Health Program, The Hospital for Sick Children, Research Institute, University of Toronto, Toronto, ON, Canada, M5G 1X8.
In type 1 diabetes, T cell-mediated death of pancreatic beta cells produces insulin deficiency. However, what attracts or restricts broadly autoreactive lymphocyte pools to the pancreas remains unclear. We report that TRPV1(+) pancreatic sensory neurons control islet inflammation and insulin resistance. Eliminating these neurons in diabetes-prone NOD mice prevents insulitis and diabetes, despite systemic persistence of pathogenic T cell pools. Insulin resistance and beta cell stress of prediabetic NOD mice are prevented when TRPV1(+) neurons are eliminated. TRPV1(NOD), localized to the Idd4.1 diabetes-risk locus, is a hypofunctional mutant, mediating depressed neurogenic inflammation. Delivering the neuropeptide substance P by intra-arterial injection into the NOD pancreas reverses abnormal insulin resistance, insulitis, and diabetes for weeks. Concordantly, insulin sensitivity is enhanced in trpv1(-/-) mice, whereas insulitis/diabetes-resistant NODxB6Idd4-congenic mice, carrying wild-type TRPV1, show restored TRPV1 function and insulin sensitivity. Our data uncover a fundamental role for insulin-responsive TRPV1(+) sensory neurons in beta cell function and diabetes pathoetiology.
PMID: 17174891

4. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1996 Jun;18(3):183-8
The role of substance P in the spinal dorsal horn in the pathogenesis of autoimmune diseases
Chen J, Li S, Liu Y, Wu S, Ji H.
Institute of Basic Medical Sciences, CAMS, Beijing.
The aim of the present study is to explore the role of immunosuppression mediated by substance P (SP) in spinal dorsal horn (SDH) in the pathogenesis of the autoimmune diseases. The experimental allergic neuritis (EAN), experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) animal models were established in the guinea pigs and Wistar rats, respectively. The effects of alteration of SP activity in SDH on immune responses and the pathogenesis of the autoimmune diseases were observed. The results showed that decreasing activity of SP in SDH by pretreatment of capsaicin or intrathecal SP antagonist could enhance cellular and humoral immune responses and aggravate the autoimmune diseases, while intrathecal SP agonist could suppress the immunity and alleviate clinical signs. The contents of SP in SDH was elevated dramatically at the peak of immune responses. These results suggest that SDH SP might participate in the pathogenesis of the autoimmune diseases. The increase of SP contents in SDH may inhibit the immune system via unknown pathway and ease clinical severity of the autoimmune disease, where SP might act as neurotransmitter in the immunoregulation of the negative feedback. To elevate SP content in SDH might be beneficial to the autoimmune diseases.
PMID: 9388989

5. Neuropeptides. 1991 Oct;20(2):73-8
Substance P and neurodegenerative disorders. A speculative review.
Barker R.
Department of Experimental Psychology, Cambridge, UK.
The causes of the neurodegenerative disorders of Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are unknown. It is proposed that all these disorders result primarily from a loss of trophic peptidergic neurotransmitter, possibly Substance P (SP). This loss in turn produces the classical neuronal degeneration seen in each of these diseases and occurs due to a combination of natural aging and chronic autoimmune destruction following a viral infection of the CNS, early in life. The loss is therefore slow and by the time of clinical presentation the inflammatory process is disappearing as the antigenic stimulus lessens with its removal. The implications of the theory in terms of future research and therapy are briefly discussed.
PMID: 1724684

6. http://www.links.net/vita/swat/course/shaman/heal.html
Shamans heal themselves.
By working through their own pain, they learn to help others.

wounded healin'
This appears a universal notion (if there is such a thing); from various shamanistic systems, as well as Greco-Roman mythology; I am reminded of Chiron, the wounded healer centaur:
"Hercules chased the maurauders all the way to Cape Malea, where Chiron himself was struck by one of Hercules' poisoned arrows, after it had passed through another centaur. The wound would have been fatal, but since Chiron was an immortal, he couldn't die of the wound, and its pain led him to a search for healing. In his search for a cure for his own wound, Chiron was the discoverer of medicine, which he taught to Asclepius."
- Chiron Mythology
In other cultures, particularly Siberian proto-Shamanic systems, healing proficiency is predicated on individual wounding and self-curation.
"But the primitive magician, the medicine man, or the shaman is not only a sick man; he is, above all, a sick man who has been cured, who has succeeded in curing himself."
- Mircea Eliade, Shamanism, page 27
Without delving into a world of detail, this preliminary sickness seems less than infectious. Perhaps the resulting celebration of destiny determines this, regardless, the sicknesses appear spiritual in origin; resulting from the shaman's need to experience pain and heal himself to become a shaman.

I am here reminded of Saint Francis of Assisi, who after a few months of fever recovered to embrace a severe ecstatic Christian mendicant life. I don't know that he was a healer, per se, but he certainly traversed the spirit realms for folks.

Once they've had their illness, or some other form of calling to the profession, many of the early shamanistic societies elaborated a ritual of pain and health to further train the shaman, or medecine man. They set up dismemberment rituals and mythology, where budding young healers and metaphysical wanderers are hacked into pieces then taken to heavenly surgeons who put together a new and improved shaman.

and/or their relatives sit around sticking cigarette butts in them for a few days.
Through this is achieved symbolic death and mystical resurrection.

Having gone through the process successfully themselves, they are thus prepared to help others through the process.


"If they have cured themselves and are able to cure others, it is, among other things, because they know the mechanism, or rather, the theory of illness."
- Mircea Eliade, Shamanism, page 31

Shaman sickness as medical training is obviated by Eskimos;
...the Eskimo neophyte must undergo a great initiatoy ordeal. Success in obtaining this experience requires his making a long effort of physical privation and mental contemplation directed to gaining the ability to see himself as a skeleton.
- Mircea Eliade, Shamanism, page 62

7. http://artscenecal.com/ArticlesFile/Archive/Articles2005/Articles0205/BTSmithA.html
BARBARA T. SMITH
Smith set up a role reversal in this epic performance, becoming a female Odysseus, organizing a journey to faraway sites from India to Norway (where she entered into the mythology of her personal ancestry in a journey paralleling Odysseus’ trip into the Underworld). Kit Galloway and Sherrie Rabinowitz of The Electronic Café International, set up communications between Smith and her partner, Dr. Roy Walford, a medical officer sealed in Biosphere 2 who became the male counterpart of Penelope. In an essay written for High Performance in 1987, Smith eerily predicted concerns she would carry on her Odyssey, including threats to life on the planet “that made the link between feminism, spirituality and ecology an obvious one,” and pleas for “the widespread recognition of the need and desire for an entirely new perception and method of living--capturing the power of the sun.”

Interlacing video projections with ephemera from the performances allows viewers’ to come closer to experiencing the cyclical and transformative nature of Smith’s work. But it is the catalog essays that enrich materials available in the gallery and compel deeper deliberation. Jennie Klein elaborates on Smith’s role as shaman.

8. http://www.grg.org/RWalford.htm
In a career that can only be described as colorful, Walford alternated years of intensive laboratory research on mice with yearlong sabbaticals in which he walked across India in a loincloth measuring the rectal temperatures of holy men, traversed the African continent on foot and lived in Biosphere 2, practicing what he called the Signpost Theory of Life..."I find it useful to punctuate time with dangerous and eccentric activities."

His most recent idea was that the immune system malfunctions during aging, producing an inappropriate response to pathogens that is manifested as the normal side effects of aging. ...

Upon graduation, what he later described as his periodic craziness took over, and he and Hibbs decided they wanted to sail around the world. Lacking money, a boat or the desire to earn the money working, they decided to try gambling. Analyzing roulette wheels, they found that each had its own idiosyncrasy, with certain numbers appearing more often than others. Armed with their observations and a borrowed $200, they tackled Las Vegas and Reno. They came away with $42,000, which allowed them to purchase the yacht of their dreams.

In addition to being a gifted scientist, Walford was also what one friend called a "cultural provocateur." Although he was on the clinical faculty at UCLA, he traveled with the Living Theater, writing reviews for the now-defunct Los Angeles Free Press. He wrote about the underground drug scene in Amsterdam before it became well known. His tastes were eclectic. He was close friends with members of the pop group Manhattan Transfer and "was into punk rock before the rest of us knew what it was about," UCLA's Cochran said. His adventures in India, Africa and Biosphere-2 got him elected to the Explorers Club.

He met and married Martha Sylvia Schwalb while he was in Chicago and they had three children, but the couple divorced after 20 years. After that, he gained notoriety for his large number of relationships with women. Friends joked that he wanted to extend his life span only because "there were too many women and too little time." Even so, he was a devoted father, his daughter Lisa said. "I majored in dance at UCLA, and he came to every performance I was in," she said. "He was my best friend."

Nerissa