timeline of pain theories from Edward Perl, Ideas about Pain

Timeline History of Pain Theories

The term for pain appeared for the first time in the ancient medical book Huang Di Nei Jing (Book on amazon.com) more than 3000 years ago, translated into English as The Yellow Emperor’s Classic of Internal Medicine by Veith in 1966 and The Medical Classic of the Yellow Emperor by Zhu in 2001. Pain was believed to be a result of imbalance between yin and yang.

Homer (8th century/700 BC) who described pain as “arrows shot by Gods. The description of pain appeared for the first time in Homer’s epics, the Iliad and the Odyssey, from around the 8th century BC in ancient Greece.

 Hippocrates (460 – 370 BC) believed that pain was caused by an imbalance in the vital fluids of a human. Hippocrate, who explicitly considered that the brain was the source of “our pains, grief, anxieties and tears” (Hippocrates, in: W.H.S. Jones (Ed.), The Sacred Disease, vol. 2, The Loeb Classical Library, Cambridge, 1923 (amazon.com)

Aristotle (384 BC – 322 BC) stated that Pain was due to evil spirits and that the gods entered the body during injury. The brain was not believed to have any direct influence and for years the liver or heart was considered to be the center for pain control. Aristotle did not include a sense of pain when he enumerated the five senses; he, like Plato before him, saw pain and pleasure not as sensations but as emotions (“passions of the soul”). implicated the heart as the central organ for the sensation of pain. He was the principal advocate of the cardio-centric theory of the soul. Aristotle considered the heart to be the seat of feelings and pain was an emotion.

China, Hua Tuo (145–208), Chinese physician, administered a herbal concoction called ‘mafeisan’ (the ingredients were cannabis in wine), to patients receiving surgery. History of pain theories (PDF)Jun Chen.

Galen (130–201) recognized the brain as the site of feeling and placed pain into the sphere of
sensation. By carefully observing patients suffering from various pain problems, he proposed that pain is a specific characteristic of the tactile sensation which corresponds to the phenomenon of allodynia (now referred to as a painful sensation caused by a previously non-painful stimulus in a pathological state). Galen also described inflammation as characterized by pain (dolor), heat (calor), redness (rubor), and swelling (tumor). History of pain theories (PDF)Jun Chen.

The brain was the seat of perception had been postulated by a few philosophers and physicians, such as Pythagoras (570–495 BC), Anaxagoras (500–428 BC), and Galen (130–201) in ancient times, and Avicenna (980–1037) in the middle age

Avicenna (ad 980–1037), a renowned Muslim philosopher and physician, noted that, in disease, pain can dissociate from touch or temperature recognition, and proposed pain to be an independent sensation. Edward R Perl, Ideas about Pain: A Historical Review (PubMed)

1326 – Canon of Medicine and Poem of Medicine by Avicenna proposed for the first time that pain is an independent sensation that is dissociated from touch or temperature. First to formulate the specificity theory.

1596 – 1650, Rene Decartes  the father of the Cartesian Model of Pain described pain as a stimulus created by the tissues as the origin of pain and the tissues send pain messages to the brain. The mind and the body were not considered to be connected to process pain.

1664 – Treatise of Man, René Descartes theorized that the body was more similar to a machine, and that pain was a disturbance that passed down along nerve fibers until the disturbance reached the brain. 1644 – Descartes’ Principles of Philosophy (read for free on Google Books) was published, in which he discussed pain in phantom limbs. From his observations, he deduced that pain was felt in the brain, not the phantom limb.

Andreas Vesalius (1514–1564), the founder of modern human anatomy, who published the classical book on the subject, On the Fabric of the Human Body did first dissections to discover that the brain was the source of pain.

1664 – Thomas Willis wrote Cerebri Anatome, recognized as the discoverer of the ‘circle of Willis’, was a pioneer of brain anatomy. Thomas Willis and the background to Cerebri Anatome
Read on Google Books

1752 – at the University of Göttingen, Albrecht von Haller published his thesis (De partibus corporis humani sensibilibus et irritabilibus (www.archive.org) discussing the distinction between “sensibility” and “irritability” in organs, suggesting that nerves were “sensible” because of a person’s ability to perceive contact while muscles were “irritable” because the fiber could measurably shorten on its own, regardless of a person’s perception, when excited by a foreign body. Later in 1757, he conducted a famous series of experiments to distinguish between nerve impulses and muscular contractions. von Haller’s work was the beginning of what we now consider “myofascial” pain.

1794 – Zoonomia; or the Laws of Organic Life (Full text on Google Books), Erasmus Darwin supported the idea advanced in Plato’s Timaeus, that pain is not a unique sensory modality, but an emotional state produced by stronger than normal stimuli such as intense light, pressure or temperature.

According to our general doctrine of sensation, parts of the body which are easily moved readily transmit the motion to the mind; but parts which are not easily moved have no effect upon the patient. Plato. Timaeus.

1880s History of Pain Theories

1811 – Charles Bell (1774–1842), a Scottish physician and anatomist, described in his privately circulated book, An Idea of a New Anatomy of the Brain (available for free on Journal of Anatomy/PubMedCentral) , that the dorsal and ventral roots of the spinal nerves serve different functions and there are different kinds of sensory receptors, each adapted to respond to only one stimulus type. He proposed that the dorsal and ventral spinal roots differ in function, with
the ventral roots being responsible for control of muscle contraction. Also Amazon Books. Specificity theory.

“Bell emphasized the involvement of the ventral roots in control of muscle contraction, but without a clear description of the functions of the dorsal roots.” History of pain theories (PDF)Jun Chen

1822 – François Magendie (1783–1855), a French physiologist, verified the sensory characteristic of the dorsal root nerve.

Magendie and Bell had a rivalry over who was the first to make this discovery. The result was the Bell-Magendie law, stating that the anterior branches of spinal nerve roots contain only motor fibers and that the posterior roots contain only sensory fibers and that nerve impulses are conducted in only one direction in each case. This was confirmed by Johannes Muller. 

The foundations of neuroanatomy on which Bell and Magendie built their research was formed two millennia in advance. Exploration of the work of four ancient scholars–Herophilus, Erasistratus, Aretaeus, and Galen. PubMed

1831 – Filippo Pacini, an Italian anatomist,  had isolated receptors in the nervous system which detect pressure and vibrations. Specificity theory.

1839 – Johannes Müller (1801–1858), established that a single stimulus type (e.g., a blow, electric current) can produce different sensations depending on the type of nerve stimulated, hypothesized that there is a specific energy (law of specific nerver energies), peculiar to each of five nerve types that serve Aristotle’s five senses, and that it is the type of energy that determines the type of sensation each nerve produces. He considered feelings such as itching, pleasure, pain, heat, cold and touch to be varieties of the single sense he called “feeling and touch.” Specificity theory. Müller’s doctrine ended the idea that nerves carry actual properties or incorporeal copies of the perceived object. It started the modern thought of asking the question:

Do the nervers that evoke the different qualities of touch and feeling have specific characters?

1849 – Moriz Schiff,(1823–1896),Magendie’s student, further refined the specificity theory
with his research with dogs and found that the pathway conveying information about temperature and pain differ from that of other sensations such as touch, cross in the spinal
cord, and do not ascend in the dorsal columns. Wikipedia

1852 – . Georg Meissner (German Anatomist) and Rudolf Wagner (German Anatomist) described receptors sensitive to light touch. Wikipedia . Specificity theory.

1858 – Moritz Schiff (Magendie’s student) was first to definitively formulate the specificity theory of pain when he demonstrated that touch and pain sensations traveled to the brain along separate spinal cord pathways. Wikipedia He showed that particular lesions of
the spinal cord resulted in separate and independent loss of tactile and pain-related
reactions. This led Schiff to propose pain to be an independent sensation, mirroring
conclusions reached by Avicenna a millennium earlier. Avicenna (ad 980–1037), a renowned Muslim philosopher and physician, noted that, in disease, pain can dissociate from touch or temperature recognition, and proposed pain to be an independent sensation. Edward R Perl, Ideas about Pain: A Historical Review (PubMed).

1860 – Charles Edouard Brown-Séquard (1817–1894), who published a series of results from animals and human cases with loss of pain and temperature sensibility contralateral and distal
to a transverse hemisection of the spinal cord (BrownSéquard syndrome or hemiplegia). This furthter confirmed the findings of Schiff.

1874 – German neurologist W. Erb proposed the intensity theory of pain, which, instead of considering the existence of specific organs in the body, claimed that pain was produced by stronger activation of nerves by an intense stimulus, while a weak stimulus produced non-painful sensation. The discovery of wide-dynamic-range (WDR) neurons in the dorsal horn of the spinal cord and the stimulusresponse characteristics of the visceral sensory system in
the 20th century supported the intensity theory of pain.

The Intensive Theory was first, conceptualized in the fourth century BCE by Plato in his work Timaeus (Read for free on Gutenberg Press Translator: B. Jowett), the theory defines pain, not as a unique sensory experience but rather, as an emotion that occurs when a stimulus is stronger than usual.

1878 – The dissociation of ascending pathways mediating pain and touch in the spinal cord was also more extensively confi rmed by both basic anatomical research in animals by L. Edinger
and clinical cases reported by Sir William Gower (1845–1915) History of pain theories (PDF)Jun Chen.

1882 – Magnus Blix reported that specific spots on the skin elicit sensations of either cold or heat when stimulated, and proposed that “the different sensations of cool and warm are caused by stimulation of different, specific receptors in the skin. Wikipedia. Specificity theory.

1884 – Magnus Blix (1849–1904) and Adolf Goldscheider (1858–1935) demonstrated
the mosaic of skin sensation and pain spots. History of pain theories (PDF)Jun Chen. Specificity theory.

1884 – Alfred Goldscheider confirmed the existence of distinct heat and cold sensors, by evoking heat and cold sensations using a fine needle to penetrate to and electrically stimulate different nerve trunks, bypassing their receptors. Though he failed to find specific pain sensitive spots on the skin, Goldscheider concluded in 1895 that the available evidence supported pain specificity, and held the view until a series of experiments were conducted in 1889 by Bernhard Naunyn. Wikipedia. Intensive theory.

1889 – Bernhard Naunyn had rapidly (60–600 times/second) prodded the skin of tabes dorsalis patients, below their touch threshold (e.g., with a hair), and in 6–20 seconds produced unbearable pain. He obtained similar results using other stimuli including electricity to produce rapid, sub-threshold stimulation, and concluded pain is the product of summation. Wikipedia. Intensive theory.

1894 – Goldscheider extended the intensive theory, proposing that each tactile nerve fiber can evoke three distinct qualities of sensation – tickle, touch and pain – the quality depending on the intensity of stimulation; and extended Naunyn’s summation idea, proposing that, over time, activity from peripheral fibers may accumulate in the dorsal horn of the spinal cord, and “spill over” from the peripheral fiber to a pain-signalling spinal cord fiber once a threshold of activity has been crossed. Wikipedia. Intensive theory.

1894 –1897, Max von Frey (1852–1932) further provided evidence linking specific sensory nerve endings in the skin to the sensation of pain. History of pain theories (PDF)Jun Chen. Von Frey proposed there are low threshold cutaneous spots that elicit the feeling of touch, and high threshold spots that elicit pain, and that pain is a distinct cutaneous sensation, independent of touch, heat and cold, and associated with free nerve endings. Wikipedia. Specificity theory.

1894 – The specificity theory of pain was put forth by Maximilian von Frey in 1894, proposed that there were subcutaneous receptors unique to the different types of sensory input. These receptors send messages to the brain through specific nerves. This does not explain chronic pain.

1896 –  Edward Titchener, pronounced in his 1896 textbook An Outline of Psychology, “excessive stimulation of any sense organ or direct injury to any sensory nerve occasions the common sensation of pain. (Google Books) Buy on Amazon.com

1906 – Sir Charles Scott Sherrington (1857–1952), introduced the concept of nociception which emphasized tissue injury as a common source of pain. In his book, The Integrative Action of the Nervous System(Read free on Google books) (buy Amazon reprint) , he also proposed the concept of the synapse, which led to the anatomical discovery of pre- and post-synaptic components. and the discovery of synaptic transmission and modulation in the central nervous system (CNS), a principle of brain structure and functions.

1915 – S.W. Ranson proposed that fine, unmyelinated nerve fibers were conductors of protopathic sensation. Specificity theory.

1920s – Galvanometer recordings of the action potentials by Sir Edgar Douglas Adrian
(1889–1977), co-recipient of the Nobel Prize for Physiology or Medicine in 1932 with Sir Charles Sherrington, andCRO-aided electrophysiological recordings by Erlanger,Gasser and their collaborators, identified different patterns of neural activity from primary afferent nerve fibers in response to different stimulus modalities (mechanical, thermal and chemical).

1929 – Pattern theory proposed by John Paul Nafe, an American psychologist, based on the work in the 1920s.

1953 – Willem Noordenbos observed that a signal carried from the area of injury along large diameter “touch, pressure or vibration” fibers may inhibit the signal carried by the thinner “pain” fibers — the ratio of large fiber signal to thin fiber signal determining pain intensity; hence, we rub a smack. This was taken as a demonstration that pattern of stimulation (of large and thin fibers in this instance) modulates pain intensity. Wikipedia.

1955 – DC Sinclair and G Weddell’s propsed the “peripheral pattern theory” claiming that all skin fiber endings (with the exception of those innervating hair cells) are identical, and that pain is produced by intense stimulation of these fibers.

1964 – Tsou K, Jang CS. Studies on the site of analgesic action (PDF) of morphine by intracerebral microinjection.

In 1965, Ronald Melzack and Patrick Wall (1925-2001) created the Gate Control Theory of Pain. This theory prevailed for 45 years.  Science article “Pain Mechanisms: A New Theory(PDF)” (Read full article in Archive.org)

1969 – Reynolds discovered that electrical stimulation of the PAG also resulted in strong antinociception in rats receiving surgery. Science Magazine 1969

The gate control theory proposes that there is a ‘gating’ at the first synaptic relay between primary afferents and transmission (T) cells (pain-signaling neurons) in lamina II (substantia gelatinosa, SG) of the spinal dorsal horn. The core of the theory has 3 facets.

1967 – Edward R. Perl’s and his collaborators, using a modified single fiber recording technique, reliably identifi ed a class of nociceptors innervated by either thinly myelinated or unmyelinated fibers in the cutaneous nerves of cats and monkeys. These discoveries of nociceptors in animals were soon confirmed by Torebjörk and his collaborators in conscious human subjects using psychophysical microneurography. History of pain theories (PDF)Jun Chen . ER Perl, Ideas about Pain (PubMed): A Historical Review.

1970s – Biopsychosical Model  was introduced by Dr. George Engel. His work is based upon a theory of open systems and its further generalization in General System Theory (GST), as proposed in the mid-20th century by biologists Paul Weiss and Ludwig von Bertalanffy. Pain Medicine and Its Models: Helping or Hindering? John L. Quintner

1990 – Melzak proposes the neuromatrix theory of pain which states that the perception of painful stimuli does not result from the brain’s passive registration of tissue trauma, but from its active generation of subjective experiences through a network of neurons known as the neuromatrix. Pain is an output of the brain. The brain gets signals from all parts of the body and interprets them in various ways and depends on many factors such as thoughts, emotions, movements, memories, fears, and touch.

See Diane Jacobs Google document on the Neuromatrix theory of pain.

1997 – Julius D. discovered TRPV1, a type of thermal nociceptor molecule and capsaicin receptor. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature Magazine. “Capsaicin, the main pungent ingredient in ‘hot’ chilli peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system.”

1998 – Book: The History of Pain, Roselyne Rey was a research fellow at the Centre National de la Recherche Scientifique in Paris, specializing in the history of medicine and the life sciences.

2007 – Edward R. Perl. Ideas about Pain

Timeline. Important discoveries and concepts for mechanisms related to pain over the past two centuries.

See also History of Massage

Science Literacy

Massage Therapy and Pain