Neuroscience 5c - Pain
Anil Chopra
- Define pain and its clinical manifestation
- Explain referred pain
- Explain how disease processes contributes to the different types of pain and their detrimental effects of pain
- Outline the experimental evidence for psychological involvement in the perception of pain
- Outline the evidence for the efficacy of biophysiological methods of treatment
- Relate psychological factors to the gate control theory
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of
such damage.
Stimuli that can potentially cause pain (i.e. cause depolarisation in nociceptor nerve endings).
Pressure
Heat & Cold
Chemicals
- Mustard, Chilli
- Insect bites
- Nettle Stings
Cell breakdown
- Inflammation
- Injury
- Malignant invasion
Somatic and Visceral Pain
Visceral Pain is generally referred pain. E.g. Diseases of:
Teeth pain felt in ear
Heart pain felt in left arm
Diaphragm pain felt in tip of shoulder
This is because when nociceptors on visceral organs are stimulated, the nerves travel along the same spinal pathways (Spinothalamic tracts) as somatic pain. The central nervous system can make no distinction between superficial pain and deep pain and so interprets all pain as superficial. The body has poor somatotopic organisation of the inside of compared to the outside/surface.
Reasons for Pain
-Protection of parts
-Guarding
-Charcot joints
It is not a rigid signalling system. There is often poor correlation of tissue injury and subjective symptoms:
-Pathology without pain – wartime, sports.
-Pain without pathology – headache, pelvic pain, depression
Gate Control Theory: this supports the theories of central and peripheral inhibition and states that pain is not just the sensation of pain receptor neurons, but the interaction between nociceptive neurons and non-nociceptive. It asserts that activation of nonnociceptive fibers, can interfere with signals from pain fibers, thereby inhibiting pain.
Nociceptive Pain
–Noxious stimulus present
–Originates from nociceptors
–Intact pain pathway
–Responsive to traditional analgesics:- Aspirin, Paracetamol, NSAID’s
–Nature of pain usually:
- throbbing
- aching
- constant
Neuropathic Pain
–Noxious stimulus often absent
–Originates from nervous system lesions
–Abnormal pain pathway
–Often poorly responsive to traditional analgesics
–Nature of pain usually:
- burning
- shooting
- scalding
–Affects 1% of population
It is caused generally by nerve injuries to nerve trunks or nerve endings there are a number of different examples:
Phantom limbis the perception and pain of limbs that have been amputated.
Trigeminal neuralgia is characterised by twitching and shock-like pain to the face. Its cause is unknown.
Painful neuropathies:- diabetes; amyloid; AIDS.
Reflex Sympathetic Dystrophy, causalgia, shoulder-hand syndrome and Sudek’s atrophy – severe pain following nerve section.
Can also be caused by disorders of pain suppression:
Post-herpetic neuralgia is common in 10% of people that get herpes zoster infection. It is caused by nociceptive fibres that are damaged by the Herpes Zoster virus.
Also caused by nerve inflammation:
Headache, migraine and pelvic pain.
Mechanisms of Abnormal Neuropathic Pain
Central Mechanisms
1) Central Sensitisation
The neurones at the dorsal horn become hypersensitive such that the response is out of proportion to the original stimulus. This can be caused by:
Phenotypic switching of low-threshold Aβ-fibres to express nociceptive neuropeptides.
Ectopic firing of nociceptor sensory neurones as a result of the accumulation of sodium channels in sprouting axons.
Sprouting of Aβ-fibres into the superficial laminae of the dorsal horn, so impulses are interpreted as noxious.
2) Wind Up
The response of the dorsal horn neurones increases even though the original stimulus remains unchanged. It is caused by the accumulation of slow excitatory postsynaptic currents elicited by Aβ and C-fibres causing prolonged depolarisation of dorsal horn neurones. It results in progressive increase in sensitivity to the same stimulus.
3) Disinhibition
Normally caused by nerve injury and results in loss of the inhibitory mechanisms that regulate dorsal horn transmission. It can result from
-a reduction in GABA levels
-death of inhibitory interneurons.
Peripheral Mechanisms
1) Spontaneous ectopic activity
The accumulation of sodium channels in the regenerating axons of injured nerves leads to a focus of hyperexcitability and ectopic discharges.
2) Nociceptor sensitisation
A result of neurogenic inflammation and increased exposure of sensory neurones to molecules such as nerve growth factor, ATP. Capsaicin and heat (42°C) both act through Transient Receptor Potential Vanilloid 1 (formerly VR1) receptors.
3) Pathological fibre interactions
An impulse in one fibre may activate other fibres, due to:
•Ephaptic cross-talk: an impulse from a neurone with a damaged myelin sheath may pass to a neighbouring neurone
•Crossed afterdischarges: repetitive activity in a primary afferent neurone can induce autonomous firing in groups of neighbouring neurones.
4) Hypersensitivity to catecholamines
Regenerating axons can express adrenoceptors, which render them sensitive to catecholamines. Nerve growth factor can stimulate sprouting of sympathetic fibres.
Sodium Channels
Currently there are 10 types of sodium channel. The particular one found on dorsal root ganglion neurones is Navα1.7. Its job is to amplify small changes in membrane potential.
In animals with inflammatory pain, it was seen to be over-expressed and is over-active in the condition of erythromelalgia (burning pain triggered by warmth). There is shown to be a persistent ion current in paroxysmal extreme (rectal) pain syndromes.
It shows loss of function in patients with congenital insensitivity to pain.
Treatment Options
1) Antidepressants, particularly tricyclics. These work by blocking monoamine uptake in central nervous system, blocking sodium channels and adrenergic receptors in the peripheral nervous system.
2) Opioids (Morphine, Fentanyl, Tramadol) are highly effective in the treatment of nociceptive pain, but have only moderate efficacy in neuropathic pain. This is because they enhance the inhibitory input at the dorsal horn.
3) Capsaicin is a topically administered agent derived from chilli peppers. It blocks C-fibres and reduces nociceptor sensitisation by decreasing “substance p” from nerve terminals.
4) Anticonvulsants such as carbamazepine, phenytoin, sodiumvalproate, work by blocking sodium channels in neurones, whereas gabapentin and lamotrigine block calcium channels, increase GABA (inhibitory) synthesis and reduce glutamate synthesis.
5) Local anaesthetics Intravenous infusions of lignocaine alleviate symptoms in a variety of neuropathic pain syndromes, but the effects are short-lived. Mexiletine, an orally-active lidocaine derivative, has been shown to be of benefit in painful diabetic neuropathy. These also work by inhibiting sodium channels in peripheral nerves and therefore stabilise membranes and reduce spontaneous ectopic discharges.
6) NMDA-antagonists (e.g. ketamine) in small trials only. They block the effects of glutamate at NMDA receptors, reducing central sensitisation.
7) GABA-agonists:- baclofen is effective in the treatment of trigeminal neuralgia.
8) Sympatholytics (e.g. guanethidine) Regional blocks; of doubtful value. They block sympathetic nerves and suppress hypersensitivity.