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Visceral pain - (3.5.1 - 3.5.16)

Updated: Mar 7, 2022



3.5.1 - Appreciate the taxonomy of functional gastrointestinal disorders and chronic

pelvic pain syndromes, in particular, the trend to move away from end-organ

nomenclature

  • The move from end-organ nomenclature has been driven by increasing recognition of pain as a disease state in its own right.

  • It moves away from a purely biomedical focus and searching for an alternative cause

  • Previous ICD-10 either had the clear disease, or patients were classified as having a mental disorder. This is clearly incorrect with a newer understanding of pain processes.

  • Chronic Primary pain was designed to think of conditions as having 'positive' findings rather than being diagnoses of exclusion

  • Terms such as 'nonspecific' and 'somatoform' and 'functional' are vague and practically often unhelpful

  • Avoids the dichotomy of physical vs psychological

Visceral pain in ICD-11

Either Primary or Secondary

Secondary is intially described by mechanism (e.g. inflammation, vascular, mechanical) and then from body locations





Reference: IASP Chronic Primary Pain -

 

3.5.2 Discuss the concurrence of somatic and visceral pain syndromes


These can occur together. See details below regarding referred pain

 

3.5.3 - Generally describe the innervation of the viscera within the:


Revised version


Innervation of the visceral organs occurs with sensory afferent fibres which travel with sympathetic and parasympathetic efferents. These have usual paths of travel with the long sensory afferent nerve going to the DRG and then synapsing within the dorsal horn.


Colon = Lumbar splanchnic (T10-L2) and sacral pelvic nerves (L5-S1)


Bladder = Lumbar splanchnic (T10-L2) and sacral pelvic nerves (L5-S1)

Second = Lateral spinal nucleus, superficial dorsal horn, and dorsal commissure

Third = PAG

General:

  • Viscera are innervated by TWO sets of afferent nerves that share overlapping functions

  • Visceral innervation is sparse compared to sensory innervation of other tissues

  • Most viscera are derived from midline structures so have innervation bilaterally

  • Visceral structures also can have their own neural networks e.g. the enteric nervous system

  • Transduction is thought to occur via unencapsulated 'free' nerve endings in target organs

  • Other levels of transduction are not fully understood and are complex in nature

  • Only 5-15% of spinal afferents in the spinal cord arise from the viscera

  • Most noxious stimuli to the viscera are encoded by mechanoreceptors. However, these are commonly thought to be polymodal and can respond also to thermal and/or chemical stimuli


Vagus nerve

  • The vagal nerve supplies all internal organs of the chest and abdomen and extending to some pelvic structures

  • Cell bodies of the vagus nerve are located in the nodose and rostral jugular ganglia

  • Vagal central afferents project to the nucleus of the solitary tract (The vagus nerve is LONELY and solitary)

  • Spinal afferents traverse the pre and post paravertebral ganglion en route to the spinal cord

  • They may send branches into those ganglia but otherwise traverse across

  • They then typically terminate in the superficial laminae (1 and 2) of the dorsal horn


Thorax (cardiac and non-cardiac)

- Vagal nerve

- Runs with fibres of the upper thorax T1-T5


Abdomen (including peritoneal and retroperitoneal spaces)

Greater splanchnic and small splanchnic --> Coeliac plexus --> Stomach, Oesophagus, liver, pancreas, adrenal, small intestine


Superior mesenteric ganglion supplies first part of large intestine


Inferior mesenteric ganglion supples kidney, bladder, sexual organs and large intestine/rectum


Vagus nerve also has innervation in this region


Pelvis (female and male)

Inferior mesenteric ganglion supplies Rectum, kidney, bladder, an sexual organs

Pelvic nerves (parasympathetic) supply rectum, kidney, bladder, and sexual organs


With particular reference to:


Stellate ganglion

  • Sympathetic fibres of the head, neck, heart and superior limbs

  • They arise from the first thoracic segments, ascend in the sympathetic chain, and synapse in the superior, middle, and inferior cervical ganglions

  • The stellate ganglion is the fusion of the inferior cervical ganglion and first thoracic ganglion

  • Blocks can help with sympathetically mediated pain from abnormal connections between sympathetic and sensory nervous systems


Stellate ganglion nerve block has low-quality small studies suggestion benefit for CRPS of the upper limb


Splanchnic nerves

Paired autonomic nerves carrying both visceral sympathetic and sensory fibres, except for the pelvic splanchnic that carry parasympathetic fibres


Arise from the sympathetic thoracic trunk to innervate the abdomen


They are the greater, lesser and least splanchnic nerve

Greater = T5-9

Lesser = T10-11

Least = T12


The Greater and lesser join to form the coeliac ganglion and least splanchnic nerve ends by synapsing with the renal ganglion


After the coeliac plexus they move to the organs of the foregut as the coeliac plexus


Lumbar splanchnic nerve forms branches of the L1 and L2 sympathetic chain

Go to the aortic plexus -->


Hypogastric plexus


Inferior hypogastric plexus is otherwise known as the pelvic ganglion


Ganglion impar

  • Termination of the sympathetic chains causes a fused ganglion called the ganglion impar

  • Primary visceral afferents from the perineum, distal rectum, distal urethra, vulva, perianal area and distal one-thrird of the vagina travel alongside visceral sympathetic fibres converging on the ganglion impar.

Pudendal nerve

  • S2-4 nerve that traverses the pelvis and terminates into the inferior rectal nerve, perineal nerve, and dorsal nerve of the clitoris





 

3.5.4 - Demonstrate an understanding of the neurobiology underlying:


Visceral pain

  • Visceral fibres complete sensory and efferent functions

  • They are c-fibres and thinly myelinated Adelta fibres

  • Silent Abeta fibres can become sensitised and undergo phenotypic switching in times of sensitisation

  • Can be triggered by mechanical, chemical or thermal triggers.

  • Some visceral organ pain sensations are more completely received as pain than others e.g. liver tissue pain versus bladder wall 

Visceral hyperalgesia

  • Pain or discomfort associated with non-noxious stimuli

  • E.g. Enhanced perception of afferent stimuli from the GI tract and genitourinary structures

  • Can manifest as lower thresholds, increased intensity, and/or atypical viscera-somatic referral areas

Peripheral sensitisation

Acute inflammation and tissue injury results in recruitment of previously mechano-insensitive afferent in addition to sensitisation of mechanically responsive afferents


Central sensitisation

Reduced descending inhibitory control and neuroplastic changes


Risk factors for visceral sensitisation to occur include:

  • Female sex

  • Duration of inciting event

  • Psychosocial stressors at the time

  • Psychological factors such as depression and anxiety

 

3.5.5 - Discuss current concepts of referred pain:


Mechanism of REFERRED pain:

  • Viscero-somatic convergence of afferent fibres in the dorsal horn

  • Signal misinterpreted by the brain as originating from a site distant from the original noxious stimulus

Mechanism of ALLODYNIA sensation:

  • Convergence-facilitation is where the nociceptive input from the viscera may sensitise dorsal horn neurons that also process somatic input

  • Sensitised second-order neurons are now responsible for non-noxious somatic input being perceived as painful.

Viscero-somatic

Pain felt in the skin, subcutis or muscle from a visceral source


Viscero-visceral

One sensitised organ causes sensitisation of another organ


Somato-somatic

Pain from one somatic site is also felt in a secondary somatic site

 

3.5.6 - Discuss the “brain-gut axis” and the neurohumoral functions of the gut


Gut-Brain Axis

  • Vagus nerve feedback from brain to gut (ANS, ENS, HPA axis)

  • Gut feedback to the brain - Immune, endocrine and neural pathways of feedback

Epigenetics – phenotypic expression of genes

  • Often environmental changes

  • Methylation can be induced by maternal neglect, emotional deprivation etc

  • Widespread changes in the glial cells and other CNS cells

  • Can impact upon the way we behave and perceive the world

 

3.5.7 - Elicit a history of painful visceral dysfunction, including but not limited to:

  Dysuria - Painful urination

  Dyschezia - Painful defecation

  Dysmenorrhoea - Painful periods

  Dyspareunia - Painful sexual intercourse

 

3.5.8 - Identify ‘red flag’ features that suggest active visceral disease.

  • Weight loss

  • Night sweats

  • Severe fatigue

  • Night pain

  • Visible blood e.g. PV, PR

  • Anaemia and iron deficiency

 

3.5.9 - Distinguish clinically between:



Active visceral nociception


  Visceral hyperalgesia

  Referred pain with and without hyperalgesia:

o Viscero-somatic

o Viscero-visceral

 

3.5.10 - Demonstrate a mechanistic approach to identifying non-visceral causes of

thoracic, abdominal and pelvic pain, especially post-surgical neuropathic

pain.


Differential diagnosis for non-visceral pain felt in visceral organ areas:

Neurological

  • Radiculopathy

  • Herpes Zoster

  • Abdominal migraine

  • Tabes Dorsalis

Haematological

  • HSP

  • Sickle Cell crises

Metabolic/Endocrinological

  • DKA

  • Acute porphyria

  • Lead poisoning

  • Addison's disease

  • Hypercalcaemia

  • Uraemia

Cancer related

  • Metastatic bone disease

  • MMyeloma

MSK

Psychological

  • Panic attacks

  • FND

Iatrogenic

  • Post surgical syndromes

  • Post-thoracotomy syndrome

  • Post-sternotomy syndreom

  • Post-mastectomy pain

  • Post-Caesarian section pain

  • Post-inguinal surgery pain

Radiation related

Chemotherapy related

Myopathy


Chronic post-surgical pain mechanisms

  • Massive injury signal followed by quiescence in peripheral nerve

  • Neurochemical release with biochemical and morphological CNS changes (plasticity)

  • Sprouting and microneuromata formation (microneuromata can ectopically fire and over-respond to low-threshold stimuli)

  • A basket-like spiderwebs of sympathetic nerves grown around the DRG sensitising them

  • New dendritic growths cause rewiring and convergence

 

3.5.11 - Demonstrate a mechanistic approach to differentiating causes of pain at the

somatic-visceral interface of the pelvis and perineum, in female and in male

patients.


Uncertain exactly what this is asking.

  • Remember that visceral pain is poorly localised commonly

  • True visceral pain is dull/colicky but can transform to sharp

  • Abdominal - worse with eating

  • Pelvic - Worse with urination, sexual intercourse, or defecation

  • Important to ask - Dysautonomia - Nausea, vomiting, pallor, diaphoresis, restlessness

 

3.5.12 - Discuss the principles of pharmacotherapy for visceral pain and visceral

hyperalgesia.


  • Evidence in these groups is weak and there are few studies demonstrating benefit for monotherapy

  • The UPOINT system has been suggested: Urinary, psychosocial, organ-specific, infection, neurologic/systemic and muscle tenderness.


Specific medications and therapies depend upon the condition but may include:

  • Antispasmodics (peppermint oil)

  • Hormonal treatments (female)

  • NSAIDs, paracetamol can be considered

  • Gabapentinoids, TCAs, SNRIs (<-- if evidence of neuropathic),

  • Ketamine and lignocaine infusions can be considered

  • Topical agents are an option

  • Opioids are last line pharmacologically

  • NB: TCA for chronic pelvic pain in women NNT = 3 (Cochrane review)

 

3.5.13 - Discuss the evidence base for the indications, effectiveness and adverse

effects of invasive therapies used for chronic visceral pain.


No evidence for much

SCS - For unrelenting angina

Neurolytic coeliac plexus block for pancreatic cancer ??Chronic pancreatitis

?? Sacral nerve stim for IBS - fairly unclear

Painful bladder syndrome - MAYBE some sacral neuromodulation evidence

Hysterectomy for pelvic pain - 30% are unhappy with the outcome

Neuromodulation for pelvic pain is unclear

Sacral neuromodulation may have benefit in pudendal neuralgia

Chronic prostatitis - Cochrane review suggested pregabalin no better than placebo

 

3.15.14 - Discuss treatment options for capsular pain associated with liver, spleen and

renal pathology.


Dexamethasone has been used in these settings

Could not find anything more specific

 

3.5.15 - Discuss the role of exogenous gonadal hormones in the treatment of

gynaecological visceral pain.

  • OCP - Helpful for endometriosis but limited evidence for non-cyclic pain

  • Cochrane review suggested moderate evidence in progesterone treatment for chronic pelvic pain (Depo IM every 12 weeks)

  • If endometriosis-injectable GNRH-agonist (e.g. gosrelin (zoladex) can provide longer-lasting effects) - Primarily used prior to surgery

 

3.5.16 - Discuss treatment options for the management of irritable bowel syndrome


Suspected IBS pathophysiology:

1. GI motility disorder with altered serotonin signalling

2. Visceral hypersensitivity disorder triggering sensitised nociceptors in gut wall

3. Intestinal barrier disorder with loss of tight-junctions. Inflammatory responses ++

4. Bile acids may affect intestinal permeability in response to different foods

5. Increased intestinal permeability following acute gastroenteritis from infection

6. Bacterial overgrowth

7. Intestinal microbiota imbalance with gut-brain communication complications

8. Low grade mucosal inflammation

9. Genetics contribution


Definition (Rome 4 criteria)

Recurrent abdominal pain 1 day/week over last 3 months with 2 or more of the following:

· Related to defecation

· Associated with change in frequency of stool

· Change in form of stool

Criteria filled for last 3 months and symptoms for 6

Subtypes

· Constipation, diarrhoea, or mixed, or unspecified


Management:

Management directed towards possible alterations in gastrointestinal flora, abnormal colonic transit time, and visceral hyperactivity.


Diet and Lifestyle interventions.


Evidence Summary

FODMAPS NNT = 2.2

General dietary change NNT = 9

Psyllium addition for 12 weeks NNT = 4-7

Probiotics NNT = 7

Antispasmodics NNT = 5

Peppermint oil NNT = 2.5

TCAs NNT = 4

SNRI NNT = 4

Rifaximin NNT = 10

(Camilleri M. (2018). Management Options for Irritable Bowel Syndrome. Mayo Clinic proceedings, 93(12), 1858–1872. https://doi.org/10.1016/j.mayocp.2018.04.032)



Specific foods/substances

•Gluten •Caffeine

•Fibre - conflicting evidence •Carbonated drinks

•Excessive Alcohol: rectal urgency •Smoking/Chewing gum (swallowed air)

•Gas-producing foods (beans, onions, celery, cabbage, Brussel sprouts)


FODMAPS: Fermentable Oligo-Di- Mono - Saccharides and Polyols:

Galactans: legumes Mannitol: corn sugar

Lactose: milk Sorbitol: corn sugar

Fructose: fruits Xylitol: corn sugar


Comorbid conditions

Comorbidities are twice as common as controls and are correlated with

  • More health-seeking

  • Worse prognosis

  • Higher rates of anxiety and depression.

Non-Pharmacological:

Acupuncture – equivocal (Cochrane)


Medication: Cochrane data...


Herbal preparations (data hard to interpret): complementary, alternative - unclear


Antispasmodics:

  • Peppermint oil NNT 2.5, hyoscine, dicycloverine, cimetropium

  • Acetylcholine competitors are more effective than placebo.

Antidepressants:

  • TCA NNT 4

  • SSRI’s 3.5

Anti- diarrhoeal

  • Loperamide avoid


No indication for benzodiazepines


Alter the flora of the large intestine - rifaximin (non absorbable antibiotic)

Two weeks treatment  significant symptom improvement at 4 and 12 weeks

Probiotic (live or attenuated bacteria)

  • Anti-inflammatory effect.

  • Bifidobacteria show a trend towards benefit.

Analgesics

  • Little or no evidence for opioids - too many side effects, no pain reduction, and no functional or quality of life improvement.

Psychological intervention

  • Only marginally greater than placebo

  • CBT, hypnotherapy and multicomponent psychological therapy being more effective than relaxation therapy and self-administered CBT.

Behavioural intervention

  • Physical exercise as a group activity beneficial in coexisting chronic fatigue and FM symptoms of IBS

  • Sleep hygiene is beneficial but evidence for specific interventions is unclear. Melatonin may be of some benefit in women more than placebo.

Pain and symptom related education

  • In a group setting was related to higher rates of symptoms resolution

 



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