TCA and managment of Chronic (prolonged) pain

TCA and managment of Chronic (prolonged) pain

Chronic pain:
Prolonged pain is the result of temporary or permanent changes in and around the peripheral and central nervous systems. Common changes are related to tissue injury, often mediated by inflammation. Tissue injury releases multiple mediators, which proliferate the pain alarm in complex cascades. The pain of inflammation and injury is
usually limited and resolves as the injury heals. However, inflammation and injury are always accompanied by changes in the peripheral and central nervous systems. Peripheral nociceptors (pain fibers) become sensitized and more readily transduce pain signals and may do so in response to a lower-intensity stimulus than before the injury(e.g. A striking example of sensitization is sunburned skin, in which severe pain can be produced by a gentle slap on the back or a warm shower) . This can result in continuous spontaneous pain, as well as pain upon movement or manipulation of the injured tissues (incident pain). Adjacent uninjured tissues are recruited by neurons in the spinal cord in a phenomenon known as secondary hyperalgesia. If these changes persist after the initial inflammatory response resolves, the pain becomes chronic. Prolonged pain can be the result of ongoing tissue injury with normal nociception or due to nerve injury with abnormal nociception (neuropathic pain). In inflammatory and neuropathic pain, reactions to mild stimuli are out of proportion to the stimuli. Such evoked stimulus induced reactions are termed allodynia, hyperalgesia, and hyperpathia.
Allodynia is pain caused by a normally nonpainful stimulus. An example is sunburn.
Hyperalgesia is an exaggerated painful sensation caused by a normally painful mechanical or thermal stimulus. For example, a gentle pinprick is usually barely painful but can be very painful in a hyperalgesic area. In this condition, the threshold of firing
for the dorsal horn neurons is lowered by the continuous input of spontaneously firing C-fibers. This may result in increased excitability of the central nervous system, a process that is broadly termed central sensitization. In other words, the dorsal horn neurons respond to normally painful inputs in a sensitized fashion, potentially manifesting as amplified pain sensitivity or expression. This may be seen as enlargement of the area in the periphery where a stimulus will trigger pain or sensation.
Hyperpathia is an abnormally painful and prolonged reaction to a stimulus. For example, a single pinprick may cause minimal pain, but with repetitive pinpricks patients describe the pain as explosive and worsening as time passes. The worsening pain represents either summation or after sensations. Summation is the perception of increasing pain or sensation to a fixed repetitive stimulus with no change in the stimulus pattern or intensity. After sensations are persistent painful sensations that are felt even after the stimulus is removed.
Role of depression: Because depression is the most common emotional disturbance in patients with chronic pain(85% of chronic pain patients have depression), patients should be questioned about their mood, appetite, sleep patterns, and daily activity. A simple standardized questionnaire, such as the Beck Depression Inventory, can be a useful screening device. It is important to remember that major depression is a common, treatable, and potentially fatal illness.


Tricyclic antidepressant (TCA):
TCAs (amitriptyline, imipramine, nortriptyline, desipramine) are extremely useful for the management of patients with chronic pain. Although developed for the treatment of depression (Their therapeutic effects are attributed to inhibition of norepinephrine and serotonin reuptake at synapses) , the tricyclics have a spectrum of dose-related biologic activities that include the production of analgesia in a variety of clinical conditions. Although the mechanism is unknown, the analgesic effect of TCAs has a more rapid onset and occurs at a lower dose than is typically required for the treatment of depression. Furthermore, patients with chronic pain who are not depressed obtain pain relief with antidepressants. There is evidence that tricyclic drugs potentiate opioid analgesia, so they may be useful adjuncts for the treatment of severe persistent pain such as occurs with malignant tumors. TCAs are of particular value in the management of neuropathic pain such as occurs in diabetic neuropathy and postherpetic neuralgia, for which there are few other therapeutic options.
Painful Conditions that Respond to Tricyclic Antidepressants


Postherpetic neuralgiaa


Diabetic neuropathya


Tension headachea


Migraine headachea

Rheumatoid arthritisa,b

Chronic low back painb


Cancer
Central post-stroke pain
aControlled trials demonstrate analgesia.
bControlled studies indicate benefit but not analgesia.
The TCAs that have been shown to relieve pain have significant side effects. Some of these side effects, such as orthostatic hypotension, drowsiness, cardiac conduction delay, memory impairment, constipation, and urinary retention, are particularly problematic in elderly patients, and several are additive to the side effects of opioid analgesics. The serotonin-selective reuptake inhibitors such as fluoxetine (Prozac) have fewer and less serious side effects than TCAs, but they are much less effective for relieving pain. It is of interest that venlafaxine (Effexor) and duloxetine (Cymbalta), which are nontricyclic antidepressants that block both serotonin and norepinephrine reuptake, appear to retain most of the pain-relieving effect of TCAs with a side-effect profile more like that of the serotonin-selective reuptake inhibitors. These drugs may be particularly useful in patients who cannot tolerate the side effects of tricyclics.