The gate control theory of pain is the idea that physical pain is not a direct result of activation of pain receptor neurons, but rather its perception is modulated by interaction between different neurons.

Pain Gate Theory:  small diameter nerve fibres carry pain stimuli through a ‘gate mechanism’ but larger diameter nerve fibres going through the same gate can inhibit the transmission of the smaller nerves carrying the pain signal.  Chemicals released as a response to the pain stimuli also influence whether the gate is open or closed for the brain to receive the pain signal. 

The interplay among these connections determines when painful stimuli go to the brain:

1. When no input comes in, the inhibitory neuron prevents the projection neuron from sending signals to the brain (gate is closed).
2. Normal somatosensory input happens when there is more large-fiber stimulation (or only large-fiber stimulation). Both the inhibitory neuron and the projection neuron are stimulated, but the inhibitory neuron prevents the projection neuron from sending signals to the brain (gate is closed).
3. Nociception (pain reception) happens when there is more small-fiber stimulation or only small-fiber stimulation. This inactivates the inhibitory neuron, and the projection neuron sends signals to the brain informing it of pain (gate is open).

Gate opened or closed by 3 factors

Conditions that open or close the gate

	Conditions that open the gate	Conditions that close the gate
Physical conditions	Extent of the injury	Medication
	Inappropriate activity level	Counterstimulation, eg massage
Emotional Conditions	Anxiety or worry	Positive emotions
	Tension	Relaxation
	Depression	Rest
Mental conditions	Focusing on the pain	Intense concentration or distraction
	Boredom	Involvement and interest in life activities

THE PHYSIOLOGY OF PAIN

The organic (disease) side of the pain continuum

This involves some stimulus to the bodies pain receptors and transmission of the pain experience through special nerve pathways to the brain.

Pain Receptors

These are bare sensory nerve endings that network throughout all organs and tissues of the body (except the brain)

They respond to many types of stimuli eg extremes of temperature, lacerations, or anything that is potentially damaging to the tissue.When actual injury occurs, Bradykinin (the most potent pain producing chemical/enzyme known) is released from the damaged cells. This bradykinin attaches to the pain receptors (free nerve endings) causing them to transmit pain impulses.

Neural Pathways in Pain

These painful impulses travel to the central nervous system through two different fibres

1. The fibres that transmit impulses quickly are called A-delta fibres. The types of sensations they carry are localised, sharp, pricking, brief sensations.

2. The fibres that transmit impulses more slowly are called C fibres. The types of sensations they carry are dull, burning, aching, longer lasting sensations.

Both these fibres send impulses by releasing a transmission agent called Substance P. Both fibres (A-delta and C) follow a similar pathway up the spinal cord until they reach the Brain   C fibres end in the lower regions of the forebrain whereas a-delta fibres go straight onto the motor and sensory areas of the cortex.

The lower regions of the forebrain do not assess the pain signals as dramatically as the motor and sensory areas of the cortex. The cortex provides immediate attention for the sharp localised pain signals, whereas the c fibres carrying dull aching pain signals are assessed more from an emotional/motivational perspective in the forebrain.

Painful impulses from the pain receptors only reach the brain if the “gate” is open.Three variables control this gate1.A-Delta fibres (sharp pain)2.C fibres (dull pain)3. A-Beta fibres that carry messages of light touchSpecial neurons located in the grey matter of the spinal cord make up the gate This gate has the ability to block the signals from the a-delta and c-delta fibres preventing them from reaching the brain.The special neurons in the spinal cord are inhibitory ie they keep the gate closed. These special neurons make a pain blocking agent called enkephalin. This is an opiate substance similar to heroin which can block Substance P the neurotransmitter from the C fibres and the A-delta fibres and this keeps the gate closed.C-Fibres and A-Delta fibres obstruct (inhibitory) the special gate neurons and tend to open the gate. A-beta fibres are irritable (excitatory) to the special gate neurons and tend to keep the gate closed.

If impulses in the C and A-Delta Fibres are stronger than the A-beta Fibres the gate opens. A-delta fibres are always stronger.

Specialised nerve impulses arise in the brain itself and travel down the spinal cord to influence the gate. This is called the central control trigger and it can send both obstructive and irritable messages to the gate sensitizing it to either C or A-beta fibres.
e.g. if the central control sensitizes the gate to C fibres (dull pain) it is more likely to open. If it sensitises to A-Beta fibres (light touch) it is more likely to close.

Hence cognitive processors influence the transmission of pain
Cognitive processors that open the gate:
* Anxiety
* Tension
* Depression eg persons having surgery
* focusing on pain
Cognitive processors that close the gate
* Happiness
* Optimism
* Distraction
* Concentration eg footballer, soldiers.
In summary whether or not pain impulses are received by the brain is dependent on a combination of the following
1.The strength of the C fibre impulses (opening the gate)
2. The strength of the A-beta fibre impulses (closing the gate)
3. The central control trigger’s sensitization of the gate to C or A-beta Fibres (to either open or close the gate)Eg rubbing area after a bump reduces the pain by stimulating the a-beta fibres of light touch to close the gate. (Theoretically)Gate control theory is the most comprehensive and widely accepted theory at present.

It is generally recognised that the ‘Pain gate‘ can be shut by stimulating nerves responsible for carrying the touch signal (mechaoreceptors) which enables the relief of pain through massage techniques, rubbing, and also the application of wheat bags and ice packs.

The Gate can also be shut by stimulating the release of endogenous opioids which are opioid (pain-relieving) type chemicals released by the body in response to pain stimuli.  Acupuncture and electrical analgesia (TENS) is thought to stimulate their release as a response to stimulation, the opioids then inhibiting the transmission of pain signals in the substantia gelatinosa part of the spinal cord – what is often referred to as the spinal root part of the nerve.

Evidence on the Gate-Control Theory

Reynolds (1969) found that rats electrically stimulated in the periaqueductal gray area were able to tolerate pain (a clamp applied to their tails). Morphine works by acting directly on the periaqueductal gray area. It is thought this area works by sending signals down from the brain in order to close the gate.

Stimulation to the brainstem is known as stimulation-produced analgesia (SPA). Pain fibres produce substance P, in order for the pain signal to cross the nerve synapse. SPA causes another chemical to block substance P.

The body produces endogenous opioids that act as a natural analgesic. Endogenous opioids can be tested by using naloxone. This drug can counteract the analgesia produced by the endogenous opioids. It is thought the endogenous opioids can be produced by electrical stimulation-produced analgesia (SPA). Naloxone blocks the analgesic effect of SPA so it is thought that endogenous opioids are produced by SPA (Akil et al 1976). Injecting Naloxone into patients after dental treatment increases their pain (Levine et al 1978). Naloxone does not always block SPA, it depends upon where the electrical stimulation is applied within the periaqueductal grey area.

Melzack and Wall conclude:

1. There are several descending control systems, some are sensitive to naloxone, but others are not.
2. Many other non-opioid transmitters, such as noradrenalin, acetylcholine and dopamine are also involved in analgesia.

The effect of endogenous opioids on pain may be dependent upon how long the pain lasts. Morphine taken to relieve short episodes of pain, tolerance develops quickly. When morphine is given to patients suffering from long-term pain (e.g. cancer) they do not develop tolerance (Melzack and Wall, 1982).

In times of stress, for example in sport or on the battlefield, endogenous opioids are released (Bloom et al 1985). This will explain why soldiers can fight on with little pain, even though they are severely injured.

 Rubbing an injured area often helps to relieve the pain. Rubbing stimulates vibration receptors, sending signals to the dorsal horn via large diameter A-beta fibres.

Physicians treat pain in numerous ways. Pain management can include medications, surgery, alternative procedures (like hypnosis, acupuncture, massage therapy and biofeedback) or combinations of these approaches.

Different types of pain medications act at different places in the pain pathways. The type of medication depends upon the source of the pain, the level of discomfort and possible side effects.

• Non-opioid analgesics, like aspirin, acetaminophen (Tylenol), ibuprofen (Advil), and naproxen (Aleve), act at the site of pain. The damaged tissue releases enzymes that stimulate local pain receptors. Non-opioid analgesics interfere with the enzymes and reduce inflammation and pain. They can have some adverse effects in the liver and kidneys and can cause gastrointestinal discomfort and bleeding with prolonged use.
• Opioid analgesics act on synaptic transmission in various parts of the central nervous system by binding to natural opioid receptors. They inhibit ascending pathways of pain perception and activate descending pathways. Opioid analgesics are used for higher levels of pain relief — they include morphine, meripidine (Demerol), propoxyphene (Darvon), fentanyl, oxycodone (OxyContin) and codeine. They can be easily overdosed and become addictive.

Pain Assessment There is no absolute measurement of the degree of pain. As we said in the beginning, pain is subjective. Numerical rating scales ask patients to judge their pain intensity on a scale from zero (no pain at all) to 10 (unimaginable pain). Doctors often use picture scales with children — they show faces with varying degrees of pain expressions. Physicians also consider a patient’s history of pain in their assessment.

• Adjuvant analgesics (co-analgesics) are primarily used for treating some other condition, but they also relieve pain. These compounds are useful in treating neuropathic pain (chronic pain that comes from injury to the central nervous system). They include the following:
• • Anti-epileptic drugs reduce membrane excitability and action potential conduction in neurons of the central nervous system.
  • Tricyclic antidepressants affect synaptic transmission of serotonin and norepinephrine neurons in the central nervous system, thereby affecting pain-modulating pathways.
  • Anesthetics block action potential transmission by interfering with sodium and potassium channels in nerve cell membranes. Examples include lidocaine, novocaine and benzocaine.

Surgery
In extreme cases, surgeons may have to sever pain pathways by altering areas of the brain associated with pain perception — or performing a rhizotomy (which destroys portions of peripheral nerves) or a chordotomy (destroys ascending tracts in the spinal cord). These surgeries are usually a last resort.

Surgical interventions can be aimed at eradicating the source of the pain. For example, many people suffer back pain from herniated disks between the vertebrae. An inflamed disc can compress a nerve and cause neuropathic pain. If the patient does not respond to medication, a surgeon might try to remove at least part of the disc and relieve pressure on the nerve.

Pain Gate Theory:  small diameter nerve fibres carry pain stimuli through a ‘gate mechanism’ but larger diameter nerve fibres going through the same gate can inhibit the transmission of the smaller nerves carrying the pain signal.  Chemicals released as a response to the pain stimuli also influence whether the gate is open or closed for the brain to receive the pain signal. 

The interplay among these connections determines when painful stimuli go to the brain:

1. When no input comes in, the inhibitory neuron prevents the projection neuron from sending signals to the brain (gate is closed).
2. Normal somatosensory input happens when there is more large-fiber stimulation (or only large-fiber stimulation). Both the inhibitory neuron and the projection neuron are stimulated, but the inhibitory neuron prevents the projection neuron from sending signals to the brain (gate is closed).
3. Nociception (pain reception) happens when there is more small-fiber stimulation or only small-fiber stimulation. This inactivates the inhibitory neuron, and the projection neuron sends signals to the brain informing it of pain (gate is open).

Gate opened or closed by 3 factors

Conditions that open or close the gate

	Conditions that open the gate	Conditions that close the gate
Physical conditions	Extent of the injury	Medication
	Inappropriate activity level	Counterstimulation, eg massage
Emotional Conditions	Anxiety or worry	Positive emotions
	Tension	Relaxation
	Depression	Rest
Mental conditions	Focusing on the pain	Intense concentration or distraction
	Boredom	Involvement and interest in life activities

THE PHYSIOLOGY OF PAIN

The organic (disease) side of the pain continuum

This involves some stimulus to the bodies pain receptors and transmission of the pain experience through special nerve pathways to the brain.

Pain Receptors

These are bare sensory nerve endings that network throughout all organs and tissues of the body (except the brain)

They respond to many types of stimuli eg extremes of temperature, lacerations, or anything that is potentially damaging to the tissue.When actual injury occurs, Bradykinin (the most potent pain producing chemical/enzyme known) is released from the damaged cells. This bradykinin attaches to the pain receptors (free nerve endings) causing them to transmit pain impulses.

Neural Pathways in Pain

These painful impulses travel to the central nervous system through two different fibres

1. The fibres that transmit impulses quickly are called A-delta fibres. The types of sensations they carry are localised, sharp, pricking, brief sensations.

2. The fibres that transmit impulses more slowly are called C fibres. The types of sensations they carry are dull, burning, aching, longer lasting sensations.

Both these fibres send impulses by releasing a transmission agent called Substance P. Both fibres (A-delta and C) follow a similar pathway up the spinal cord until they reach the Brain   C fibres end in the lower regions of the forebrain whereas a-delta fibres go straight onto the motor and sensory areas of the cortex.

The lower regions of the forebrain do not assess the pain signals as dramatically as the motor and sensory areas of the cortex. The cortex provides immediate attention for the sharp localised pain signals, whereas the c fibres carrying dull aching pain signals are assessed more from an emotional/motivational perspective in the forebrain.

Painful impulses from the pain receptors only reach the brain if the “gate” is open.Three variables control this gate1.A-Delta fibres (sharp pain)2.C fibres (dull pain)3. A-Beta fibres that carry messages of light touchSpecial neurons located in the grey matter of the spinal cord make up the gate This gate has the ability to block the signals from the a-delta and c-delta fibres preventing them from reaching the brain.The special neurons in the spinal cord are inhibitory ie they keep the gate closed. These special neurons make a pain blocking agent called enkephalin. This is an opiate substance similar to heroin which can block Substance P the neurotransmitter from the C fibres and the A-delta fibres and this keeps the gate closed.C-Fibres and A-Delta fibres obstruct (inhibitory) the special gate neurons and tend to open the gate. A-beta fibres are irritable (excitatory) to the special gate neurons and tend to keep the gate closed.
If impulses in the C and A-Delta Fibres are stronger than the A-beta Fibres the gate opens. A-delta fibres are always stronger.

Specialised nerve impulses arise in the brain itself and travel down the spinal cord to influence the gate. This is called the central control trigger and it can send both obstructive and irritable messages to the gate sensitizing it to either C or A-beta fibres.

e.g. if the central control sensitizes the gate to C fibres (dull pain) it is more likely to open. If it sensitises to A-Beta fibres (light touch) it is more likely to close.

Hence cognitive processors influence the transmission of pain Cognitive processors that open the gate:
* Anxiety
* Tension
* Depression eg persons having surgery
* focusing on pain
Cognitive processors that close the gate
* Happiness
* Optimism
* Distraction
* Concentration eg footballer, soldiers.

In summary whether or not pain impulses are received by the brain is dependent on a combination of the following
1.The strength of the C fibre impulses (opening the gate)
2. The strength of the A-beta fibre impulses (closing the gate)
3. The central control trigger’s sensitization of the gate to C or A-beta Fibres (to either open or close the gate)Eg rubbing area after a bump reduces the pain by stimulating the a-beta fibres of light touch to close the gate. (Theoretically)Gate control theory is the most comprehensive and widely accepted theory at present.

It is generally recognised that the ‘Pain gate‘ can be shut by stimulating nerves responsible for carrying the touch signal (mechaoreceptors) which enables the relief of pain through massage techniques, rubbing, and also the application of wheat bags and ice packs.

The Gate can also be shut by stimulating the release of endogenous opioids which are opioid (pain-relieving) type chemicals released by the body in response to pain stimuli.  Acupuncture and electrical analgesia (TENS) is thought to stimulate their release as a response to stimulation, the opioids then inhibiting the transmission of pain signals in the substantia gelatinosa part of the spinal cord – what is often referred to as the spinal root part of the nerve.

Evidence on the Gate-Control Theory

Reynolds (1969) found that rats electrically stimulated in the periaqueductal gray area were able to tolerate pain (a clamp applied to their tails). Morphine works by acting directly on the periaqueductal gray area. It is thought this area works by sending signals down from the brain in order to close the gate.

Stimulation to the brainstem is known as stimulation-produced analgesia (SPA). Pain fibres produce substance P, in order for the pain signal to cross the nerve synapse. SPA causes another chemical to block substance P.

The body produces endogenous opioids that act as a natural analgesic. Endogenous opioids can be tested by using naloxone. This drug can counteract the analgesia produced by the endogenous opioids. It is thought the endogenous opioids can be produced by electrical stimulation-produced analgesia (SPA). Naloxone blocks the analgesic effect of SPA so it is thought that endogenous opioids are produced by SPA (Akil et al 1976). Injecting Naloxone into patients after dental treatment increases their pain (Levine et al 1978). Naloxone does not always block SPA, it depends upon where the electrical stimulation is applied within the periaqueductal grey area.

Melzack and Wall conclude:

1. There are several descending control systems, some are sensitive to naloxone, but others are not.
2. Many other non-opioid transmitters, such as noradrenalin, acetylcholine and dopamine are also involved in analgesia.

The effect of endogenous opioids on pain may be dependent upon how long the pain lasts. Morphine taken to relieve short episodes of pain, tolerance develops quickly. When morphine is given to patients suffering from long-term pain (e.g. cancer) they do not develop tolerance (Melzack and Wall, 1982).

In times of stress, for example in sport or on the battlefield, endogenous opioids are released (Bloom et al 1985). This will explain why soldiers can fight on with little pain, even though they are severely injured.

 Rubbing an injured area often helps to relieve the pain. Rubbing stimulates vibration receptors, sending signals to the dorsal horn via large diameter A-beta fibres.

Physicians treat pain in numerous ways. Pain management can include medications, surgery, alternative procedures (like hypnosis, acupuncture, massage therapy and biofeedback) or combinations of these approaches.

Today's Pain Theory

Wilhelm Erb's (1874) early pattern theory hypothesis, that a pain signal can be generated by intense enough stimulation of any sensory receptor, has been soundly disproved. The thin (A-delta and C) peripheral nerve fibers carry information regarding the state of the body to the spinal cord. Some of these thin fibers do not differentiate noxious from non-noxious stimuli, while others, nociceptors, respond only to painfully intense stimuli.

Because the A-delta fiber is thinly sheathed in an electrically insulating material (myelin), it carries its signal faster (2.5–35 m/s) than the unmyelinated C fiber (0.5–2.0 m/s). Pain evoked by the (faster) A-delta fibers is described as sharp and is felt first. This is followed by a duller pain, often described as burning, carried by the C fibers.

Spinal cord fibers dedicated to carrying A-delta fiber pain signals, and others dedicated to carrying C fiber pain signals up the spinal cord to the thalamus in the brain have been identified. Pain-related activity in the thalamus spreads to the insular cortex (thought to embody, among other things, the feeling that distinguishes pain from other homeostatic emotions such as itch and nausea) and anterior cingulate cortex (thought to embody, among other things, the motivational element of pain); and pain that is distinctly located also activates the primary and secondary somatosensory cortices.

One study has found that pain reduction due to non-noxious touch or vibration can result from activity within the cerebral cortex, with minimal contribution at the spinal level.Melzack and Casey's 1968 picture of the dimensions of pain is as influential today as ever, firmly framing theory and guiding research in the functional neuroanatomy and psychology of pain.