Saturday, December 28, 2013

Pain and depression medications

So if your doctor suggests putting you on an antidepressant to help with your chronic pain, should you be offended, thinking they're saying that you don't really have a reason for pain? Should you look at them like they've just reenacted the scene from Moonstruck?

Before you do, let's look at it a little first. Pain is a complex process.

How does pain work?

First you have a source of stimuli (an injury, inflammation, infection, etc)- these are called noxious stimuli. Appropriate name I say! "There are three categories of noxious stimuli:
The injured cells release certain chemicals that lets your system know it needs some help there. "This noxious stimulation causes a release of chemical mediators from the damaged cells including:

These chemicals activate special nerves, called nociceptors, which send a signal to your brain via the spinal cord. When this signal reaches the spinal cord it determines whether immediate action is necessary- like if you stick your finger on a hot oven and you jerk it away- your instant reflexes are from your spinal cord. Even if the spinal cord signals you to jerk your finger away, that signal still travels to your brain. Now up until it reaches the brain, your body uses special fibres to differentiate the type of pain or "stimuli" called C fibres and A delta fibres.

C fibresA-delta fibres
Receptor type:
  • Polymodal respond to more than one type of noxious stimuli:
  • Mechanical
  • Thermal
  • Chemical
Pain quality:
  • Diffuse
  • Dull
  • Burning
  • Aching
  • Referred to as ‘slow’ or second’ pain
Receptor type:
  • High-threshold mechanoreceptors respond mechanical stimuli over a certain intensity.
Pain quality:
  • Well-localised
  • Sharp
  • Stinging
  • Pricking
  • Referred to as ‘fast’ or ‘first’ pain   

Once the signals get to the brain, certain neurotransmitters take over. "In order for the pain impulses to be transmitted across the synaptic cleft to the NDHN, excitatory neurotransmitters are released, which bind to specific receptors in the NDHN. These neurotransmitters are:
  • adenosine triphosphate;
  • glutamate;
  • calcitonin gene-related peptide;
  • bradykinin;
  • nitrous oxide;
  • substance P.
"The pain impulse is then transmitted from the spinal cord to the brain stem and thalamus via two main nociceptive ascending pathways. These are the spinothalamic pathway and the spinoparabrachial pathway. The brain does not have a discrete pain centre, so when impulses arrive in the thalamus they are directed to multiple areas in the brain where they are processed."

[Side note: "Neurotransmitters are biochemical messengers that carry pain signals from one nerve cell to the next. The three main neurotransmitters that send pain signals to the brain are substance P, NMDA (n-methyl-d-aspartate), and glutamate. Excess amounts of these chemicals, especially substance P, make it easier for pain signals to reach the brain."]

So, the signal goes to your thalamus to be directed to different areas for a complete analysis. Think of it like the CSI tv shows- everything gets analyzed! ("New imaging techniques have mapped out at least 200 areas of the brain that respond to different types of pain."  Your brain keeps and catalogs everything about that pain experience- how was it compared to other pain, what was happening at the time, how quickly did it resolve, any complications.... Your brain is a pack rat of 1930's Depression baby quality-- "I might need this one day..."! Because the thalamus sends the signal to be analyzed by different areas of the brain, you experience pain in several different ways. "Perception of pain is the end result of the neuronal activity of pain transmission and where pain becomes a conscious multidimensional experience. The multidimensional experience of pain has affective-motivational, sensory-discriminative, emotional and behavioural components."

"The modulation of pain involves changing or inhibiting transmission of pain impulses in the spinal cord. The multiple, complex pathways involved in the modulation of pain are referred to as the descending modulatory pain pathways (DMPP) and these can lead to either an increase in the transmission of pain impulses (excitatory) or a decrease in transmission (inhibition).
Descending inhibition involves the release of inhibitory neurotransmitters that block or partially block the transmission of pain impulses, and therefore produce analgesia. Inhibitory neurotransmitters involved with the modulation of pain include:
  • endogenous opioids (enkephalins and endorphins);
  • serotonin (5-HT);
  • norepinephirine (noradrenalin);
  • gamma-aminobutyric acid (GABA);
  • neurotensin;
  • acetylcholine;
  • oxytocin.
Endogenous pain modulation helps to explain the wide variations in the perception of pain in different people as individuals produce different amounts of inhibitory neurotransmitters. Endogenous opioids are found throughout the central nervous system (CNS) and prevent the release of some excitatory neurotransmitters, for example, substance P, therefore, inhibiting the transmission of pain impulses."

(Notice that serotonin and norepinephrine in there? That helps inhibit pain signals from reaching the brain? Remember that!)

After an injury is healed the nociceptors should stop firing. However if they are constantly excited, like in endo, you get chronic pain. Sometimes even once an area is healed, the nociceptors will keep firing.

"The exact mechanisms involved in the pathophysiology of chronic pain are complex and remain unclear. It is believed that following injury, rapid and long-term changes occur in parts of the CNS that are involved in the transmission and modulation of pain (nociceptive information) (Ko and Zhuo, 2004). A central mechanism in the spinal cord, called ‘wind-up’, also referred to as hypersensitivity or hyperexcitability, may occur. Wind-up occurs when repeated, prolonged, noxious stimulation causes the dorsal horn neurones to transmit progressively increasing numbers of pain impulses."

"The gate theory says that as these pain messages come into the spinal cord and the central nervous system (before they even get to the brain), they can be amplified, turned down or even blocked out. There are many accounts of how people injured on the battlefield or in sports games don’t feel any pain from their injuries until afterwards. This has to do with the brain being busy doing other things and shutting the gate until it can pay attention to the messages. Large diameter nerve fibres (A-beta fibres) responsible for transmitting signals of touch to the brain have the ability to close the pain gate and so block signals from other smaller diameter nerve fibres which transmit pain. An example of this would be when a child falls over and hurts her knee — if she rubs her knee, the signal from that sensation of touch temporarily blocks the pain signal travelling from the injured knee to the brain....

"At the cellular level, several processes can contribute to pain becoming chronic.
  • Pain receptors and neurones along the pain pathway may become too easily activated.
  • Connections between the neurons in the pathway can be altered.
  • The brain and spinal cord may fail to dampen down the pain signals.
  • Pain receptors that are normally silent (dormant) can become activated by inflammation.
  • After nerve injury, nerves may regrow but function abnormally.
Chronic pain can persist for months or even years after an initial injury and can be difficult to treat. People with chronic pain may experience sleeplessness, anxiety and depression, all of which can compound the problem."

Now to tie in that thing about serotonin and norepinephrine helping block pain signals and depression medications:

"Clinical symptoms of depression can be grouped into three basic categories: emotional (depressed mood, lack of motivation, disinterest in social activity, anxiety), cognitive (inability to concentrate, poor memory), and physical (insomnia, headache, fatigue, and stomach, back, and neck pain)....Theories about the biologic basis for depression have evolved over more than 25 years. The principal biochemical basis for depression has focused on two neurotransmitters: serotonin and norepinephrine.[9,10] These two neurotransmitters have also been implicated in the underlying pathophysiology of chronic pain.[4–7] Serotonergic and norepinephrine neurons overlap in the brain, and these two systems interact biochemically and neuroanatomically. In patients with depression, alterations or reductions of these two neurotransmitters and their respective receptors become dysfunctional over time, leading to a dysregulated system....

"The link between the higher brain centers involved with depression and pain and the peripheral body regions occurs in the brain stem, with neurotransmission relayed through the spinal cord. Abnormal body activity and functions (e.g., musculoskeletal) are suppressed from the consciousness by the serotonin and norepinephrine descending pathways in the spinal cord that originate in the brain stem.[12,13] ...A painful stimulus from the periphery can affect multiple pathways, eliciting the complex set of mechanisms leading to and found within the central nervous system....

"As stated earlier, numerous receptor systems located on these two nociceptor pathways exist that form the starting point of pain and its interactions with depression. Glutamate, a major excitatory neurotransmitter, affects both pathways and could serve as one common pharmacologic model for the rapid action of the Ad fibers and the slower actions of C fibers.[5] Many other receptor systems and their corresponding stimuli complete this discussion of the circuitry of pain modulation that incorporates depressive symptomatology. This discussion focuses only on serotonin and norepinephrine pathways. Other models are certainly involved, most notably, enkephalin and opioid peptide links....

"For many years, antidepressants have been used in different chronic pain syndromes with or without the presence of clinical depression....The studies also indicated that the antidepressant's beneficial effect on pain does not seem to be related to its effect on mood....Based on the interrelationship between pain and depression, the serotonin and norepinephrine reuptake inhibitors (SNRIs) may be preferred over other antidepressant pharmacologic classes (e.g., selective serotonin reuptake inhibitors [SSRIs]) because of their dual action on noradrenergic (norepinephrine) and serotonergic (serotonin) activities in the central nervous system. Animal models have shown a dose-dependent response with SNRIs' ability to decrease pain sensitivity, whereas SSRIs were ineffective....Most of the above-mentioned clinical trials were conducted mainly with duloxetine and other agents in a double-blind, placebo-controlled environment. These studies demonstrate that antidepressants are safe and effective treatments of physical painful symptoms whether or not comorbid depression and/or anxiety are present for a relatively short time period of up to 12 weeks. An early response was noted during the first few weeks, with continued benefits throughout the study."

"Physical pain and depression have a deeper biological connection than simple cause and effect; the neurotransmitters that influence both pain and mood are serotonin and norepinephrine. Dysregulation of these transmitters is linked to both depression and pain. Antidepressants that inhibit the reuptake of both serotonin and norepinephrine may be used as first-line treatments in depressed patients who present with physical symptoms."

[Lengthy quote below is courtesy of]

"Living with chronic pain should be enough of a burden for anybody. But pile on depression -- one of the most common problems faced by people with chronic pain -- and that burden gets even heavier.
Depression can magnify pain and make it harder to cope. The good news is that chronic pain and depression aren't inseparable. Effective treatments can relieve depression and can help make chronic pain more tolerable....
"Pain provokes an emotional response in everyone. Anxiety, irritability, and agitation -- all these are normal feelings when we're hurting. Normally, as pain subsides, so does the stressful response.
But what if the pain doesn't go away? Over time, the constantly activated stress response can cause multiple problems associated with depression. Those problems can include:
  • chronic anxiety
  • confused thinking
  • fatigue
  • irritability
  • sleep disturbances
  • weight gain or loss
"Some of the overlap between depression and chronic pain can be explained by biology. Depression and chronic pain share some of the same neurotransmitters -- the chemical messengers traveling between nerves.  They also share some of the same nerve pathways. The impact of chronic pain on a person's life overall also contributes to depression. 'The real pain comes from the losses' caused by chronic pain, according to Feinberg. 'Losing a job, losing respect as a functional person, loss of sexual relations, all these make people depressed.' Once depression sets in, it magnifies the pain that is already there. 'Depression adds a double whammy to chronic pain by reducing the ability to cope,' says Beverly E. Thorn, professor of psychology at the University of Alabama and author of the book Cognitive Therapy for Chronic Pain....
"The fact that chronic pain and depression involve the same nerves and neurotransmitters means that antidepressants can be used to improve both chronic pain and depression. 'People hate to hear, 'it's all in your head.' But the reality is, the experience of pain is in your head,' says Feinberg. 'Antidepressants work on the brain to reduce the perception of pain.' Tricyclic antidepressants have abundant evidence of effectiveness. However, because of side effects their use is often limited. Some newer antidepressants are prescribed by doctors to treat certain painful chronic syndromes and seem to work well with fewer side effects. 
      Physical Activity    
"Many people with chronic pain avoid exercise. 'They can't differentiate chronic pain from the 'good hurt' of exercise,' says Feinberg. But, the less you do, the more out of shape you become. That means you have a higher risk of injury and worsened pain. The key is to break this cycle. 'We now know that gentle, regular physical activity is a crucial part of managing chronic pain,' says Thorn. Everyone with chronic pain can and should do some kind of exercise. Consult with a physician to design an exercise plan that's safe and effective for you. Exercise is also proven to help depression. 'Physical activity releases the same kind of brain chemicals that antidepressant medications release -- [it's] a natural antidepressant,' says Thorn."
So, yes, antidepressants could help improve your pain levels. If you think about it, things that increase the good/helpful neurotransmitters and decrease the excitatory/make ya hurt neurotransmitters like eating healthy (think lots of fresh fruits, veggies, omega 3's, etc etc, less processed food) and exercise (yay endorphins!) and things that help control your stress (yoga, meditation, something that makes you laugh) can help too. So, remember to make taking time to take care of yourself a priority. If you don't, you will have a hard time taking care of the ones you love. So take care of yourself for their sake! :)