Posted on August 30, 2016February 17, 2023 by Ashley Davidoff

Pain, Pain -Go Away!

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You came with no warning and no invitation

You came with a single message of doom and gloom

I had no control

It was fate

It was no joke

I had to take you seriously

You seem to be endless and to be going nowhere

With the unintended intention to taunt and haunt me

You are the source of my suffering.

Since the dawn of man

You have accompanied us with a not so gentle reminder

That everything is not OK

Some say you are protective

But it is sometimes hard to understand

All I know is that I suffer

Nociceptors sense the feeling

They come in different forms

Transmitting pain from pressure, prick, or improper heat,

– or a severe lack of it

Quickly the sensation travels

On the A, delta, or C train-

Impulses that run their course

From source to spinal cord

With sizzling hot news of my experience

Where they snap to a halt as they clap as a synapse

And get a second order of direction

At the gate of decision

Which waves them on to a new thoughtless action

On their way to master control.

And through and via the wire of the RAS

Which awakens an awareness of you;

And then to the thalamic relay

Where they get their new orders:

To whom they should turn

And what direction to take.

In the higher levels of limbic autonomic and homunculus centers

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The sense becomes real

And the feeling becomes severe

And after all the science

I know not what to do

But to increase my heart rate a little,

Contract a muscle and a gland or two

And perhaps let out a scream at the height –

And impugn your intrusive impudence that imposes on me.

pain, nociceptor, poem, prayer, sensory system, thalamus, A fiber, delta fiber, C fiber, Ashley Davidoff MD. The Common Vein, Art in Anatomy

And then sometimes

We use the eyes and guise

Of X-ray Eyes

Or try a tincture of opiate

To extirpate the excruciate –

And then sometimes to no avail

Yet I could care less about your wonderful pathways of biology and science

I know that I hurt -but also in a different way

It is not only the pain that I feel

But the pain of fate as well

That was handed to me as a card in a bad deal of nature

And I have no choice but to deal with it …..

But it hurts!

person, old lady, emotional pain, aging, poverty, loneliness

See the BLOG about the Art and Science of Pain

Ashley Davidoff MD

Revised since publication as a Blog August 2016

Posted on August 29, 2016February 17, 2023 by Ashley Davidoff

Pain – Art and Science

Pain

Pain is an unpleasant sensation originating from our physical and or emotional environments.

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Faces of Pain

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Extreme Physical Pain

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Extreme Emotional Pain

Physical Pain

Pain is a symptom and as such reflects a derangement of either the external or internal environment.

All sensations start by stimulating a receptor of a nerve that conducts the impulse to the spinal cord where low level control and discrimination occurs, and transfers the stimulus to the brain, where higher centers process the stimulus and react to it. The structures in the brain include the thalamus, somatosensory cortex, limbic system, and autonomic systems and they are involved in perception, localization and integration. They send out a stimulus with instructions of how to react which is executed by muscle contraction or tissue secretion.

Functionally, pain is protective. The physiology and pathophysiology relate to changing the mechanical stimulus into an electrical impulse, and then through a series of complex synapses the stimulus is transmitted with the intent of protecting the person from further damage.

The causes of pain are innumerable and exist within the full spectrum of human diseases. Pain may result from pain receptors sensitive to pain, (pricking, cutting, tearing) extreme temperatures, pressure, or aberrant chemical environments. A myriad of processes then occur in response to tissue injury causing either irritation of a somatic nerve or distension and pressure on a visceral sensory nerve. Inflammation is one of the most common of these injurious processes that is classically and universally expressed with pain – a concept first described by the second century philosopher Celsus.

The result of a pain impulse is usually withdrawal from the insulting stimulus, resting of the injured part, or seeking the help of a medical practitioner if the pain is unbearable and arises from an internal disorder.

Diagnosis of pain disorders should proceed with careful history taking and clinical examination, followed by appropriate laboratory tests, and imaging if necessary.

Pain is a very common symptom and most instances are treated with an analgesic or antiinflammatory agent. For more serious pains, treatment is directed at the cause of the pain.

Classification

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The table explores the variety of ways of classifying pain. The left hand column reveals the classification based on functionality, origin, mode of stimulation, pathological causes and relationship of pain to chronicity. As for functionality it may be adaptive or nonadaptive. The pain may originate from somatic or visceral nociceptors, may originate from damaged nerves in which case it is called neuropathic, or it may be psychogenic. The causes are usually via the inflammatory process but may result from any of the disease listed.

Structural Basis of Pain

A pain impulse is initiated by sensory receptors called nociceptors which are located in almost all the tissues. A noxious stimulus say from a hand touching a hot stove is then transmitted by sensory nerves to the spinal cord where a direct spinal reflex causes immediate withdrawal from the source. Additionally the stimulus is modified in the spinal cord by a variety of influences from other sources and is then transmitted via the midbrain and reticular activating system to the cortex. Finally, the stimulus reaches the brain’s somatosensory area where it is perceived and localized with additional extension to other areas of the cortex for the provision of a variety of protective reactions to the stimulus.

We will now expand the detail of the structural pathway described above.

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Pain from the Joints

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Pain from Sinuses

The Sensory Pain Receptors – Nociceptors

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Nociceptor

A pain impulse is initiated by sensory receptors called nociceptors which are located in almost all the tissues. They are tree like branching structures.

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Types of Receptors Subtending the A delta Fibers and C Fibers

The diagram shows sensory stimuli including sharp pressure, extreme heat and cold as well as chemical, stimulating the free nerve endings of the nociceptors that are linked to the myelinated A delta fiber , and non myelinated C fiber. The myelinated fiber will conduct the impulse between 3 and 15 times faster than the non myelinated fiber.

These specialized receptors vary in structure and number throughout the tissue and viscera of the body. There are external nociceptors that are situated in the skin and cornea with higher concentrations in the coverings of the body including the skin, pleura, pericardium, peritoneum and periosteum. Internal nociceptors are found in muscles, joints, around blood vessels, and within the mucosa of some organs including the urinary bladder, genitourinary tract, and the gastrointestinal tract. There are nociceptors in varying concentrations in almost every organ in the body, but interestingly there are none in the brain substance itself .

First Order of Transmitting Sensory Fibers

The first order of nerve fibers transport the stimulus from the nociceptor to the dorsal root ganglion

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The sensory receptors of the nociceptors are found in the tissues peripherally and are connected by a long fiber that transmits the impulse to the ganglion cell that lies in the dorsal ganglion in the neural canal alongside the spinal cord. This diagram shows the three types of receptors and fibers that transmit impulses related directly and indirectly to pain . The upper fiber is called the C fiber and it is non myelinated, consists of the receptors in the top left hand corner that when stimulated transmit the impulse via a long afferent neuron to the cell body lying alongside the spinal column. This fiber is relatively thin, measuring between .4 to 1.2 micrometers, and conducts the impulse at about 2m/s. The second neuron is the A delta fiber and it responds to the pricking or sharp sensation that is first felt and reacted to. It is weakly myelinated and is about 2-6 micro meters thick, and conducts the stimulus with a velocity of between 15-30 meters per second. The last fiber is the A beta fiber and it is responsible for the pressure component which indirectly affects response to pain by affecting the gate mechanism of pain. It is greater than 10 microns thick due to heavier myelination and conducts impulses at 30-100 meters per second

The Dorsal Root Ganglia

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The Dorsal Root Ganglion of the Afferent Neurons

The dorsal root ganglion is a focal accumulation of the first order nerve cells of the sensory component of the peripheral nerve. (orange) It is situated in the neural foramen of the vertebral body. The central process emanates from the ganglion cell and ends in the dorsal horn.

2^nd Order of Neurons

The second order sensory fibers are those fibers in the spinal cord. They first cross to the contralateral side of the spinal cord and then connect to the thalamus via the spinothalamic tract.

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Second Order Neurons – Cross Over in the Spinal Cord and 3rd order are Found in the Spinothalamic Tract

The spinothalamic tract is the major sensory ascending pathway of 2nd order neurons and serves as the major pathway for pain, temperature, itch and crude touch. Within its construct, the spinothalamic tract has three merging bands of specialized fibers that conduct pain impulses. The anterior spinothalamic tract carries pain signals initiated by touch while the lateral spinothalamic tract carries slow and fast fibers for pain and temperature sensations. The anterolateral spinothalamic pathway, located in the anterolateral white column pathway in the anterior half of the lateral funiculus conducts a variety of somatic pain signals.

3rd Order of Neurons – Connect the Thalamus with the Sensory Cortex

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The Three Orders of Neurons

Second Order Neurons From the Spinal Cord to the Brain and Perception of the Pain The Three Orders of Neurons

The stimulus is first converted into an electrical impulse which is taken by a first order sensory nerve (orange) to the spinal cord (dorsal root ). The second order neurons (blue) first transport the stimulus to the contralateral spinothalamic tract which in turn transports the impulse to the thalamus,. The third order neurons (pink) transport the impulse to the somatosensory cortex.

Role of the Thalamus

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Thalamus – Relay Station to the Cortex in the Pain Pathway
The thalamus (T) is the gateway to the cerebral cortex. It is a paired organ and represents the main part of the diencephalon and subserves both motor and sensory function. It is structurally and functionally situated between the cortex and the midbrain. The thalamus has specific nuclei with diffuse projections to and from multiple regions of cerebral cortex. The thalamus functions as a translator for the cerebral cortex. It processes sensory and motor information and mediates the autonomic nervous system regulating sleep and arousal. The thalamus also contains reciprocal connections to the cortex that are involved in consciousness. It may also play a role in vestibular function. The thalamus translates pain signals of the 2nd order neurons and gives rise to the third order neurons that extend to the cortex. Awareness and localization of the pain is then achieved at the level of the cortex. The thalamus however is not merely a relay station for nociception but also plays a role in processing the stimulus. Axons terminating in the lateral thalamus mediate discriminative aspects of pain (somatosensory cortex) including the originating body part. The fibers ending in the medial thalamus mediate the motivational and affective aspects relating for example to the emotional and memory of pain. These third order neurons travel to the prefrontal cortex, insular and cingulate gyrus which contribute to the emotion and memorization of pain experiences.

The Homunculus Man and Localization of the Pain

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HOMUNCULUS MAN and Localization of Sensation in the Somatosensory Cortex of the Parietal Lobe

The homunculus man (literally the “little man”) is the distorted figure drawn to reflect the concept of size of organ paralleling the size of the sensory innervation. The diagram reflects the relative functional sensory space each body part occupies in the somatosensory cortex. Those structures with a high density of sensory receptors are represented by a larger size, while those with a lesser concentration of sensory apparatus are shown as being “smaller” in size. Hence the mouth lips, hands feet and genitalia have a relatively large representation. Nerve fibers from the spinothalamic tract in the spinal cord (blue line) are relayed to the thalamus (orange) which filters and then distributes the sensation to the somatosensory cortex.

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The Somatosensory Cortex in the Parietal Lobe – Home of the Sensory Homunculus

The somatosensory cortex in the parietal lobe is the location of the the main sensory receptive area for all the senses including pain. It receives the stimuli from the thalamus and then integrates the information with other parts of the brain that will modify the perception of the sensation

The function of the somatosensory cortex is that of a higher processing center for touch, temperature, pain, and proprioception serving to amplify awareness of the sensations enabled by the thalamus. Sensation from the left side of the body are processed in the right somatosensory cortex and similarly those from the right side are processed on the left. The higher function of the somatosensory cortex allows us to localize the pain to a specific site, perceive the character and intensity of the stimulus, and sometimes helps identify the shape of the originating object.

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The Higher Multicentric Levels of Pain Perception and Reaction

The somatosensory cortex relays impulses to other cerebral areas of perception that modulate the reaction to the pain It forward the pain signals via the white matter to other centers in the cortex to enable integration with visual and auditory input, and with other higher cortical functions such as emotion and memory for example. The full experience is then “seen” by the brain enabling the consequent reaction to be as discriminating and prudent relative to the nature and experience of the person. The difference between the reaction of an infant, child and an adult to the “shot at the doctors” speaks volumes about this latter function.

Emotional Pain

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Pain of Poverty

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Pain of Addiction

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Pain of Loneliness

Pain .. Pain go away! – and please leave us alone!

Posted on March 17, 2016February 17, 2023 by Ashley Davidoff

Anatomy of Endometriosis and Adenomyosis

Ashley Davidoff MD

Endometriosis is a disease caused by misplaced or ectopic endometrial tissues located beyond the uterus most commonly resulting in pain at the time of menstruation. The ectopic endometrial tissue is controlled by the oestrogen and progesterone cycles. The ectopic tissue bleeds at the time of menstruation and causes pain. Since neither the ectopic endometrium nor the blood can be extruded from the body, recurrent bleeding eventually results in scar formation which may cause non cyclical chronic pain.

Chronic Pelvic Pain is Unbearable

Endometriosis and adenomyosis cause horrific pain. For some the pain may only occur during the menstrual cycle but for others it can be constant, day and night, excruciating in nature, invading every aspect of normal daily life . Pain is a common symptom defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.” This statement characterizes the evolved nature of pain as a warning system and feedback mechanism that influences how we adapt to our environment. However, pain at its core it is suffering and its persistence can be insufferable for people and diagnostically problematic to those who care for the sick, as well being a burdensome cost to society.

The cause of endometriosis is not truly known. Long standing hypotheses include spillage of endometrial tissue into the peritoneal cavity via the fallopian tubes or transvascular spread to remote areas . More recent hypotheses include spillage of stem cells during embryonic development, metaplasia of coelomic epithelium, abnormal vasculogenesis, and environmental factors

Endometriosis occurs in 5-10% of women. When endometrial tissue is located outside of the uterus, it can cause pelvic and back pain, as well as pain with sexual intercourse (dyspareunia). It is also associated with infertility by distorting anatomy, (for example Fallopian tube adhesions) , or physiological changes that result in altered immune and hormonal environments with consequent impairment of ovum implantation .

From a structural standpoint, endometriosis most commonly affects the ovaries and Fallopian tubes but can affect any of the pelvic organs including the peritoneal cavity, bladder, ureters, bowel, broad ligaments, uterosacral ligaments, cul de sac and even the nerves. Implants range in size from small microscopic implants, but are are commonly about 1-2cm.

The Intraperitoneal Aspect of the Pelvic Cavity

The peritoneal cavity or coelomic cavity is a large cell lined space via which almost all the abdominal organs are connected . It may be considered the suburban space around which the houses of the town are positioned. The ova are released from the ovary into the peritoneal space, but they are quickly directed by the fimbriae into the Fallopian tubes.

Endometriomas

Endometriomas are large hemorrhagic cysts that occur on the ovary and may be up to to 20cms in size. They are usually round in shape, much like a large blood blister after they have bled. The nodules can be red-blue to yellow-brown in color, (chocolate cysts) and occur just below the serosa of the organ to which they are attached. As the lesions undergo recurrent hemorrhage, they can become associated with fibrosis as stated. Rarely they may be associated with malignant transformation.(<1%).

MRI of an Endometrioma

A T2 weighted image of the pelvis (left) with an overlay of colors on the right shows a 10cms endometrioma (overlaid in red) with internal debris better appreciated in the left image. The large ‘chocolate cyst” lies above the uterus (pink) and compresses the bladder (yellow)

MRI has a 90% specificity and 90% sensitivity for endometriomas. On T1 weighted images the endometriomas may be bright and do not lose signal on fat suppressed sequences. Heterogeneity is due to the presence of degraded products. Septations may also be present. Both these features are present in the above image . On T2 weighted sequences “shading” is caused by repeated episodes of bleeding reflecting hemorrhagic contents in various stages of degradation. The wall of the endometrioma may contain hemosiderin which leads to a loss of signal on the T2 weighted sequence.

Unusual Locations

Endometriosis is rarely can be more far reaching and may involve the kidneys, brain, diaphragm, and pleura. When it involves the diaphragm or pleura, shoulder pain may be associated with the entity. Pleural disease can cause life threatening catamenial pneumothorax induced by the menstrual cycle .

Endometriosis on the Bladder

A CT scan through the pelvis (left) shows an endometriotic implant on the bladder wall. The image on the right shows the endometriotic implant overlaid in maroon on the right anterior surface of the bladder (yellow overlay). The implant measures about 1.1cms. The fornix of the vagina is overlaid in pink. Most peritoneal implants are too small to be visualized by conventional imaging and require laparoscopic evaluation for diagnosis.

Endometriosis in the Skin of the Groin

A CT scan through the pelvis (left) shows an endometriotic implant in the subcutaneous region of the skin in the left inguinal region (image a, circled). The region is magnified in image b and the endometriotic deposit is labelled “e” with maroon overlay. An ultrasound of the left groin(c) shows the implanted endometriosis (black) medial to the artery (red) and vein (blue). In image d, the region of endometriosis (e) is overlaid in maroon.

Clinically the entity more commonly occurs in nulliparous women and the degree of pain is variable. As endometrial tissue, it is responsive to the cyclical hormonal fluxes, and thus may bleed in response to hormonal changes. Pain commonly occurs at the time of the menses. The volume of ectopic endometrial tissue does not correlate with the severity of the pain, but rather with the depth of infiltration into the tissue, or the degree of distension that might occur. The pain is usually recurring and commonly but not necessarily occurs during the menses. With induction of fibrosis, pain may be caused by other structural changes that are unrelated to the menses.

Diagnosis is suspected clinically and confirmed by ultrasound. When a woman in the reproductive phase of her life presents with pain, the imaging study of choice is a pelvic ultrasound. Hemorrhage into evolving follicles is a common cause of pelvic pain and these could be also quite large. This entity has to be differentiated from an endometrioma that has a characteristic ultrasonographic appearance shown below

ovary, ovaries, genitourinary tract, genitourinary system, woman, Art in Anatomy, Ashley Davidoff MD, endometriosis, endometrioma, chocolate cyst, ultrasound,

Endometrioma on Ultrasound

A transvaginal ultrasound of the adnexa shows an endometrioma with characteristic low level echoes reminiscent of the texture of the testes on ultrasound. The image on the right is an overlay in a biloculate cyst. Some through transmission is present.

Chocolate Cyst on US and CT

A 25 year old female presents with painful menses. The ultrasound shows a cystic mass in the pelvis with a large amount of debris in the cystic cavity consistent with a chocolate cyst (a). Image b is an overlay showing the fine granular appearance of the sediment. When the patient is in decubitus position (c) , the sediment settles to the dependant portions with a clear supernatant. Image (d) is a CT scan of the same patient, showing a non specific cyst in the left ovary. In this instance CT has little diagnostic value in the characterization of the abnormality other than localising a large cyst, and excluding other causes for the pain. Although the appearance on the ultrasound is consistent with endometriosis, a hemorrhagic cysts is possible and the distinction may only be made pathologically.

When a female patient in the reproductive age presents with pelvic pain and ultrasound or MRI are negative, laparoscopy is indicated both for diagnosis of small or flat lesions lesions as well as for therapy. Microscopic deposits which may cause symptoms will not be identified by imaging techniques and will only be seen laparoscopically. The reluctance to undergo an “invasive” procedure is understandable, but delaying or worse still missing the diagnosis will cause unnecessary long term suffering.

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Laparoscopy

Laparoscopic image of small blood blisters characteristic of endometriotic lesions of the pelvic wall in the peritoneum

Courtesy Author Hic et nunc. Acknowledged work is in public domain

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Blood Blisters in the Cul De Sac and Sacrouterine Ligament

Laparoscopic image of endometriotic lesions in the pouch of Douglas and on the sacrouterine ligament.
Courtesy Author Hic et nunc. Acknowledged work is in public domain

Treatment options depend on patient preference, including whether fertility is desired, but include both medical and surgical options. Medical management frequently involves suppression of regular menses/hormones . Surgical options include removal of implants or surgical induction of menopause (i.e. oophorectomy and hysterectomy).

Adenomyosis

Adenomyosis is a disease of the myometrium caused by misplaced or ectopic endometrium in the myometrium resulting in myometrial hyperplasia and smooth muscle hypertrophy clinically manifesting as pelvic pain and uterine enlargement. The entity can be focal or diffuse

Enlarged and Painful Uterus of Adenomyosis

The exact cause of the displacement is not known but it is presumed that a breach in the endometrial myometrial barrier enables a small amount of endometrium to translocate and remain viable. There is a high prevalence rate with about 40% of hysterectomy specimens displaying the entity.

The junctional zone of the uterus is the epicenter of the structural abnormality The junctional zone is subendometrial smooth muscle that is more compacted, and contains less water in comparison to the outer myometrium. (McCarthy) The junctional zone is functionally different from the outer myometrium.

The Normal Junctional Zone on MRI

The normal sagittal view of the uterus is a T2 weighted MRI from a 16 year old female with pelvic pain. The myometrium consists of an outer part (dark red) and an inner more homogeneous part called the junctional zone (light maroon) Since a T2 weighted image is sensitive to water, we understand from this image that the outer part has greater white signal and therefore contains more water, and likely more vascularity. The junctional zone (light maroon) on the contrary has less water and therefore is blacker. The endometrial canal, cervical canal and vaginal cavity are outlined in yellow and the vaginal wall is overlaid in pink.

Clinically the patient presents with pelvic pain, dysmenorrhea, menorrhagia and may contribute to infertility. On exam the uterus is enlarged.

The diagnosis is best made by MRI which shows a thickened junctional zone (>10-12mms) s. The deposition of acute blood, blood degradation products such as iron, or the presence of fluid filled microglandular deposits in the junctional zone make the MRI findings highly specific for the diagnosis.

Treatment options include pain management with NSAIDS, and hormonal manipulation. Surgery and hysterectomy is the only current option for cure.

MRI

Adenomyosis with a Thickened Junctional Zone and Enlarged Uterus

A T2 weighted MRI (a) shows fluid in the endometrial cavity, surrounded by a thick dark layer of the junctional zone, and then surrounded with a slightly brighter outer myometrium. The color overlay in b, shows a small amount of fluid in the endometrial cavity (yellow) surrounded by a thickened subendometrial junctional zone (light maroon) measuring up to 13 mms characteristic of adenomyosis. The outer myometrium (dark maroon) is normal

The junctional zone thickening is key to the diagnosis of adenomyosis on MRI. The junctional zone normally measures 8mm or less. Between 8-11mm it is considered indeterminate, and when it measures 12mm or greater, it is considered diagnostic for the disease. The junctional zone may thicken normally in the first few days of the menstrual cycle or during myometrial contractions. Cystic changes in the junctional zone are also characteristic and relatively common and represent small blood blisters. Linear striations radiating from endometrium to myometrium are also seen but these are not as easy to discern. These probably reflect a breech in the endometrium reflecting microscopic tears extending into the myometrium.

Ultrasound

The Normal Junctional Zone on Ultrasound

A transvaginal ultrasound of a premenstrual woman in the sagittal plane (left) reveals a normal view of the uterus with characteristic premenstrual appearance. Image on the right is an overlay showing the components of the endometrium and subendometrial layers. The stripe is almost homogeneously echogenic and thick but also shows a hypoechoic halo of the junctional zone or inner myometrium. (salmon) The homogeneous stripe is made up from two histological layers (barely distinguished by this ultrasound)– the inner stratum functionalis (deep orange) that will shed once the spiral arteries vasoconstrict, and the outer stratum basalis (deep yellow) that will not shed, and will be the basis for regenerating the endometrium in the next cycle. The next layer as stated above is the compact myometrium – the junctional zone (aka inner myometrium) , and is followed by the thicker outer myometrium (maroon).

The junctional zone is hypoechoic due to decreased water content, and is formed by smooth muscle cells that are tightly packed. The extracellular matrix and water content are sparse. It usually measures less than 8mm.

Adenomyosis with Ectopic Deposits in the Junctional Zone

Two echogenic nodules (overlaid in green in image on the right) are present in the subendometrial layer, (junctional zone) in a woman with menorrhagia. The nodules are in close proximity and have appositional relationships with the endometrial stripe (yellow overlay). They distort the endometrial lining. These findings likely account for the menorrhagia. Included in the differential diagnosis are dystrophic changes in prior foci of adenomyosis and submucosal fibroids. An MRI would assist to characterize the lesions in the subendometrial layer.

ART IN ANATOMY

Category: Pain

Pain, Pain -Go Away!

See the BLOG about the Art and Science of Pain

Pain – Art and Science