Annals of Indian Psychiatry

: 2017  |  Volume : 1  |  Issue : 2  |  Page : 120--123

Psychoneuroimmunological mechanisms in pain management and healing: Illustrative case series

Vidhya Annapoorni1, RN Mangual2, Chandra Retnaswami Sadanandavalli3,  
1 Department of Paediatric Surgery, SAT Hospital, Government Medical College, Trivandrum, Kerala, India
2 Department of General Surgery, MKCG Medical College, Brahmapur, Orissa, India
3 Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Correspondence Address:
Chandra Retnaswami Sadanandavalli
Faculty Block, Neurocentre, National Institute of Mental Health and Neurosciences, Bengaluru  -  560  029, Karnataka


Background: Phantom pains with no painful lesion, war wounds which are painless, and spiritual practices such as fire walking are examples of painful stimuli and pleasurable experience. Why frontal leukotomy reduces pain and not parietal lobe are questions indicating it is not the sensations that hurts. Aim and Settings: The aim of the study was to discuss the course of illness of a series of exceptional patients. Patients and Methods: Exceptional patients who astonishingly handled their pain and healed themselves are described.  The first patient, a woodcutter, carried his bowel in a bag for 4 months, the second patient had a large fungating tumor in breast, the third patient repaired his palatal cleft with paper and lived several years, and two swamijis who dissociated themselves from their malignancy. Results and Conclusions: The quality of life of these patients was excellent in spite of serious disorders which indicates “The doctor” within is the most powerful and cheapest healer.

How to cite this article:
Annapoorni V, Mangual R N, Sadanandavalli CR. Psychoneuroimmunological mechanisms in pain management and healing: Illustrative case series.Ann Indian Psychiatry 2017;1:120-123

How to cite this URL:
Annapoorni V, Mangual R N, Sadanandavalli CR. Psychoneuroimmunological mechanisms in pain management and healing: Illustrative case series. Ann Indian Psychiatry [serial online] 2017 [cited 2023 Mar 25 ];1:120-123
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Pain is defined as psychic adjuvant of an imperative protective reflex or anything the patient feels hurts. There are situations where pain becomes pleasurable such as war wounds in chest indicating the valance of the warrior and the reverse in Couvade syndrome. As these phenomena are not easily comprehensible, they are often ignored. Mind responds to perception and not reality. The percept generated by neurons produces an operational link between the stimuli and the objective world based on the experience base available. Therefore, it involves the evaluation of the sensory stimuli, its conscious feeling state, the formation of physiological and behavioral responses, and unconscious percept added to it. Thus, the unimodal processed information undergoes transformation by cross-sensory association, and cognitive network operations with attention, affect, and semantic information are added by lateral prefrontal, medial orbitofrontal, and temporal lobes.[1]

Psychology of pain

Pain has a signaling pathway transmitting signals and affective and evaluation pathway, and the neurotransmitters involved are serotonin and noradrenaline which are modifiable by mood. Pain experienced is influenced by the limbic system, the anterior cingulate, and the right ventral prefrontal cortex. Pain is amplified by social rejection, attention to pain, assumption of sick role, fear, anxiety, memory of pain and reduced by distraction, working as usual those, etc.[2],[3] Pain can sometimes be a learned response simply coming from mind.[4] For who continuously work, pain may be experienced less due to less feeling of disability.[5],[6],[7]  Cytokines and other factors released by immune cells, make nociceptor neurons release neuropeptides that modulate pain or pain related response to protect the host. Thus immune cells, glial cells and neurons act together to modulate pain, infection and inflamation.[8] Immune cells and glia act to alter pain sensitivity.

Placebos produce real measurable effects on the body by releasing various neurotransmitters such as endorphins and dopamine. Ancient Indian and Egyptian healing systems utilized the mind–body-associated healing. Sir Louis Pasteur felt at advanced age that it is not the microbe but the terrain that matters.

 Patients and Methods

Patient 1

A 34-year-old woodcutter presented with direct inguinal hernia for the past 6 years. He underwent hernioplasty with prolene mesh. (However, the patient did not come for follow-up for the next 5 months.) He came for follow-up after 5 months with the following symptoms. On the 4th day of discharge, he reported for woodcutting and noticed that the skin was giving way with blood-stained discharge and the mesh got expelled 3 weeks after surgery, and this was followed by some fleshy material seen through wound. He covered it neatly with a plastic bag and continued to work for the next 4 months. Then, the patient developed pain with swelling of the mass, vomiting, fever, and features of acute intestinal obstruction and pregangrene. He underwent emergency bowel resection anastomosis and wound repair and made an uneventful postoperative recovery. [Figure 1] shows intestines of the patient lying outside the wound in the abdomen and the plastic bag, in which he carried his bowel for 4 months by the side.{Figure 1}

Patient 2

A 65-year-old female had a swelling in her breast for 2 years. The lesion was painless but was rapidly increasing in size, and she had an ulcer over the right breast with undermined edges and base covered with slough, 30 cm × 23 cm in size, with an underlying mass occupying the entire breast with destruction of the nipple–areolar complex, firm in consistency 35 cm × 30 cm, nontender with lobulated surface, with a few discrete tender axillary lymph nodes, and foul-smelling discharge. Histopathology showed phyllodes tumor. She did not undergo further evaluation with mammogram or ultrasound. She was evaluated for fitness for surgery and after partial treatment of infection underwent mastectomy with axillary lymph node biopsy and was asymptomatic on reviews till 10th postoperative month. [Figure 2] shows the large mass in the right breast with large-area ulceration with discharge.{Figure 2}

Patient 3

This patient was a 55-year-old male who grazed cattle. He came to the hospital for treatment of episodes of loss of consciousness and tonic–clonic movements. Examination revealed nasal twang to voice, flat nasal bridge [Figure 3], and a large defect in the hard palate with clear margins. When questioned, the patient informed that he was hit by his bull on one occasion about 15 years ago and underwent treatment for the loss of consciousness at a local hospital with conservative measures. He was advised to undergo surgery for the injury of his palate. However, he treated himself with indigenous medications with which the wound healed. However, he was left with a perforated palate through which the turbinates were visible [Figure 4]. Later, he developed the habit of sealing the defect with paper to prevent food and saliva leaking into his nose [Figure 5]. He was investigated for the loss of consciousness which revealed an area of gliosis in both frontal regions and epileptic discharges arising from bifrontal focus. A diagnosis of posttraumatic epilepsy with traumatic palatal perforation was made, and the patient was not willing for treatment of the palatal defect. His computed tomography scan showed bilateral frontal lobe gliosis which was the cause for his epilepsy [Figure 6].{Figure 3}{Figure 4}{Figure 5}{Figure 6}

Patients 4 and 5

Patient 4 had difficulty walking with bladder symptoms, and investigations showed carcinoma prostrate and secondary spine. Although he cooperated for radiotherapy and surgery, he was totally unaffected and lived nearly 10 years and after achieving his set goals asked the team around him to write his age as the age in which he had predicted Samadhi and passed away. The 2nd swamiji was fully paralyzed with bedsore and stained with excreta but was working on the translation of some scriptures to regional language as if that body part did not belong to him. He also made a surprising recovery.


Our patients in this observational study uniformly showed extraordinary insensitivity to pain, infection, and inflammation and had a very good outcome too.


Psychoneuroimmunology of pain and healing by neuroimmune and endocrine links

Hypothalamus is the main transducer of information to immune system which is carried out by β-messenger molecules and immune system talks to hypothalamus by immunotransmitters.[9] Thus, there are bidirectional circuits, and ventromedial hypothalamus has a role in antibody formation. Natural healing is a powerful process existing in nature and enhanced by training, meditation, and hypnosis and “the doctor who resides inside” concept.[10] Hypothalamus can change immune responses, and lymphocytes have receptors for neurotransmitters. Thymic peptides alter the efficacy of neuroendocrine circuits, thymosin fraction 5 increases the secretion of adrenocorticotropic hormone, β-endorphins, growth hormones, prolactin, corticosteroids, and luteinizing hormone-releasing hormone, suggesting a thymus pituitary adrenal axis modified by thymosin α1 and thymus–pituitary–gonad axis by thymosin β4.[11] Leukocytes produce α, β, and γ endorphins which bind to opioid receptors even in hypophysectomized animals, suggesting their independent role in pain control.[12] Cytokines such as IL-1 can stimulate the release of corticotropin-releasing factor and astrocytes, and microglia can produce interleukin (IL-1) and completes the neuroimmune endocrine link. IL-2 induces lymphokine-activated killer cells in cancer patients[12]. Interferon-α is found to induce analgesia through opioids. Behavioral changes of immunological dysfunction are probably adaptive for restoration of homeostasis. Buddha in his Sermon on Noble Truth of pain says disciplining mind to ignore pain by gating makes the person not perceive pain. These information indicate that there is interdependence of psycho neuroimmunoendocrine functions in dealing with inflammation, pain, and healing.

With reference to patient 1, how the patient managed to carry his intestines in a polyethylene bag and continued woodcutting? How was the pain not experienced until gangrene occurred? What protected him from infection? Patient 2 could tolerate such a huge mass and also severe infection. The third patient had severe palatal injury and brain injury and it left him with minimal problems in the quality of life other than seizures. With reference to patients 4 and 5, how they switched themselves off from the disease and carried out intellectually demanding activities? It is possible that they were ignorant but what protected them from the fatal complications expected in the usual scenario. Therefore, knowledge and negative expectations probably tilt in a negative way the nature's healing process.

The first three patients were illiterate persons who were not capable of any spiritual practices. Is pain the most primitive social instrument indicating man's capacity for sacrifice? It is likely that their primitive instincts of social responsibility overtake the pain and complications through the psychoneuroimmunological mechanisms in a positive way. The results of prefrontal leukotomy in intractable pain indicate that pain is probably an emotion rather than a painful sensation. What is the role of pain anticipation in pain perception? According to Papez, cingulum sets in motion the inner emotional experience. How are the internal mechanisms modulated in perception and reactions of pain, inflammation, and infections in the wilderness? Are they naturally present in all living things until they are eliminated by conscious switching to artificial lifestyle away from nature? What is the role of functional magnetic resonance imaging in understanding these situations? Can neuroendocrine and immune markers explain these extremes of human behavior?

The factors which these ordinary people who so naturally carry in themselves without any real Sadhanas is astonishing, reaching the highest realm of metaphysical existence as a routine way of life living with nature in self-healing, distracting the mind away from the experiences of potentially painful and harmful situations, and for sustaining even apparently less spiritual levels of existence, like daily living. Therefore, it is possible to rise above being ordinary individuals in ordinary life itself and that probably is the most harmless way to manage pain and inflammation. Orbitofrontal cortex, rhinal sulcus, insular region, thalamus, and amygdala have been postulated to have an important role in deciding the outcome expectation optimizing sensory perceptions and behavior by unconscious modifications. Prognostic outcome expectations modified by response inhibition along with adaptive behaviour and judgement subconsciously mediated by the orbito frontal cortex might positively modify the patient's perception of pain in response to serious illness.

 Declaration of Patient Consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


These patients who include both the highly literate and the illiterate, who showed extraordinary skills in handling pain and infection in serious backgrounds, indicate that probably all healing mechanisms existed in nature and got erased in the evolutionary scale, when man became dependent on external tools than internal innate abilities. A relook into internal healing mechanisms might be one of the tools of the future without the bad effects of the various therapies used in dealing with serious diseases.

Limitations of the study

All patients are illustrative descriptive cases. We have not submitted them for any detailed assessment processing or questionnaire-based evaluation of their neuropsychological functions, cognitive scorings, or any serious imaging-based assessments in view of the gravity of the situation when patients were seen, lack of facility for detailed assessment, and also unwillingness of the patients to cooperate for detailed time-consuming assessments.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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