Pain post TBI

Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage…” (p.210; International Association for the Study of Pain 1994); the relationship between pain and tissue damage is not constant nor is it uniform. Pain following an injury or surgery can be either acute or chronic, and often lasts for months or years post injury. Acute pain occurs at the time of injury and although it often occurs as a one-time event, it may reoccur as a series time limited event (Gould 2007). Acute pain is usually associated with defined tissue damage or a pathological process. Chronic pain is usually defined as pain that continues for more than three to six months. Chronic pain is often not as well associated with tissue damage or a pathological process. Pain can also be defined as subacute (pain between the end of the first month post injury and six months post injury) and recurrent acute (pain that persists over an extended period of time but recurs as isolated pain episodes).

Until very recently, there has been very little information in the literature regarding the prevalence, etiology, assessment and treatment of pain post TBI (Zasler et al. 2011). This may be the result of pain syndromes being overlooked in patients with a TBI for a number of reasons (Gellman et al. 1996). Multiple etiologies including orthopedic injuries, burns, organ injuries, or central or peripheral nervous system injuries can result in acute or chronic pain in those recovering from a TBI (Ivanhoe & Hartman 2004).

Pain is believed to be more common immediately post injury (acute pain) and it is widely accepted that this pain will resolve as the damaged tissue recovers (Uomoto & Esselman 1993). The focus is on management of symptoms over a relatively short defined period of time and on assisting the healing of damaged structures. Chronic pain by its very nature may not resolve, or is very slow to resolve, and often manifests itself as post traumatic headaches (PTH), neck and shoulder pain, back pain, peripheral nerve injury, heterotopic ossification and pain related to spasticity (Hoffman et al. 2007; Lahz & Bryant 1996; Ofek & Defrin 2007). In a study conducted by Lahz and Bryant (1996), chronic pain was reported by 52% of those who were diagnosed with a moderate to severe TBI and 58% of those diagnosed with a mild TBI. Of those reporting pain, over 80% reported experiencing pain on a daily basis (Lahz & Bryant 1996). Comparable rates were given by Hoffman et al. (2007) who examined a bodily pain scale completed one year post TBI. Of the 146 individuals who participated, 74% of participants reported experiencing pain and 55% of those reported pain interfered with a variety of daily activities. Higher rates of pain were also related to gender, lower Functional Independence Measure scores, higher rates of depressive symptoms at baseline and again at one year post injury, and lower scores on the Community Integration Scale. Those who were injured in acts of violence reported experiencing greater pain (Hoffman et al. 2007). Pain is significantly associated with depression, with one study reporting rates of pain and depression as 70% and 31%, respectively and 34% and 22%, respectively at one year follow-up (Sullivan-Singh et al. 2014).

Pain related to orthopedic injuries, spasticity or heterotopic ossification will not be covered in this section. For a more detailed discussion on spasticity and treatments post ABI please see section 4.3 in this module and a detailed discussion on heterotopic ossification post ABI is available in Module 11. Due to the complexities of pain, we have decided to focus on pain post TBI specifically. The diagnosis of pain post TBI is an important part of an individual’s recovery. A lack of recognition or diagnosis of pain can lead to an increase in aggression and agitation, or an inability to participate or benefit from rehabilitation (Ivanhoe & Hartman 2004; Sherman et al. 2006). In individuals who have sustained a moderate or severe TBI, the diagnosis of pain is often made through the combination of symptoms described by the patient and information provided by family members. Pain post TBI can evolve from episodic pain to daily pain with an increasing negative impact over time; pain ultimately impacts participation in rehabilitation and thereby slows recovery (Branca & Lake 2004).

Problems associated with pain include a delay in cognitive recovery, sleep disorders and fatigue, elevated levels of anxiety and depression and post-traumatic stress disorder (Dobscha et al. 2009; Hoffman et al. 2007). Cognitive deficits associated with TBI may prevent individuals from using adaptive pain coping strategies that are critical to the management of chronic pain. When treating pain post TBI, it is important for clinicians to identify the causes of pain, not just the symptoms (Zasler et al. 2011). To reduce the impact on cognitive recovery, treatment plans should take into consideration the medications the patient is already receiving, as well as the location, type and frequency of the pain. It should be acknowledged that in many cases the pain generator persists in which case pain can only be managed. Treatment for pain often involves an interdisciplinary approach (Branca & Lake 2004). To increase the likelihood of compliance with treatments, a good working relationship between physicians and the patient is needed. 

Assessing Pain Post TBI

Pain itself is both complex and subjective; thus, self-reports are vital to any treatment plan. Descriptive details related to the intensity, the length of time the pain is felt, the location, and what exacerbates or relieves the pain are vital in order to develop an individualized treatment strategy (Zasler et al. 2011). Currently there exist a number of tools and assessments used by physicians and therapists to assist in diagnosing and measuring pain. Amongst these is the numeric rating scale (NRS), the visual analogue scale (VAS), the Headache Diary, the Headache Disability Inventory and the McGill Pain Questionnaire. 

Visual Analog Scale

The VAS is available at no cost and has been used with many adult populations to assess pain intensity. The scale is a horizontal or vertical line, usually 10 centimeters in length and is completed by the respondent. Two verbal descriptors, no pain and the worst pain imaginable, anchor the scale (Zasler et al. 2011). Generally those completing the scale are asked to describe the pain within the past 24 hours. A ruler is used to the distance between the no pain anchor and the line that the respondent has drawn. Higher scores indicate greater pain (Hawker et al. 2011).

Numeric Rating Scale (NRS)

The NRS is also commonly used to assess pain. Here the patient rates the pain they are experiencing on a scale of 0 to 10. The NRS, like the VAS, is anchored with no pain and the worst pain imaginable. Individuals are generally asked to report on pain intensity within the past 24 hours. This scale can be administered verbally or graphically. A higher score indicates higher levels of pain (Hawker et al. 2011). A 30% reduction on the NRS is clinically important and has been found to be equivalent to ratings of moderate relief or much improved (Farrar et al. 2001). 

McGill Pain Questionnaire

The McGill pain questionnaire, designed for adults with chronic pain, measures the sensory, affective and evaluative aspects of pain and pain intensity (Hawker et al. 2011). The paper and pencil questionnaire is administered by an interviewer with the respondent present. The respondent is asked questions and must select one word, from a list presented to them, which best describes their present pain. If the pain an individual is feeling cannot be described by the words presented to them, then no word is selected. Scores are based on the number of words selected with higher scores indicating greater levels of pain.

Headache Disability Inventory

The headache disability inventory was designed to measure the impact of headaches on
activities of daily living (Jacobson et al. 1994). This self-report scale consists of 25 items designed to probe the functional and emotional aspects of headache. Items are measured as either a yes or no. The scale has been found to be easy to complete, simple to score and interpret (Jacobson et al. 1994). 

Headache Diary

Those who are asked to maintain a headache diary are required to log their headaches on a daily basis. Recorded in the diary is the time of day the headache begins, the intensity of the pain, any medication being taken, and any triggers for the headache. Additionally, individuals are asked to record alcohol consumed, periods of fasting, foods eaten, sleep patterns, weather, stress levels, emotional ups and downs, and women are asked to record the date of their menstrual cycle (Arnstein 2004). A variety of headache diaries or headache calendars are currently available. These diaries potentially allow the patient to gain better control over their pain, by identifying its potential causes, and provide feedback regarding treatment efficacy (Branca & Lake 2004). 

Pain Syndromes Post ABI

Neuropathic Pain

Neuropathic pain is initiated or caused by a primary lesion or by dysfunction of the nervous system (International Association for the Study of Pain 1994). Peripheral nervous system pain can result from mechanical trauma, metabolic disease, neurotoxic chemicals, infection, or tumor (Costigan et al. 2009; O'Connor & Dworkin 2009). Central nervous system pain may be associated with spinal cord injury, stroke, TBI or multiple sclerosis (Costigan et al. 2009). Neuropathic pain can result from compression of peripheral nerves when patients are immobilized for long periods of time. A diagnosis of neuropathic pain is often based on careful medical evaluation (careful history, physical and neurological exams, MRI findings, blood and serologic tests) (Dworkin et al. 2003). Treatment remains a challenge, as even effective treatments offer only partial pain relief (Finnerup et al. 2005). Pharmacological treatments for neuropathic pain include: amitriptyline, pregabalin, gabapentin, duloxetine, carbamazepine, lidocaine and opioids (Waszkielewicz et al. 2011). When considering treatments it is important to keep in mind the safety and efficacy of these drugs; particularly how they interact with other medications and how they will impact neurological recovery post TBI. 

Central Pain Syndromes

Zaslar et al. (2012) have defined central pain as “pain associated with lesions of the central nervous system” (p 967). Treatments are limited in number and efficacy (Nicholson 2004); the goal is often a reduction in pain and not complete relief. For example, studies have examined the effects of lidocaine and IV morphine but the results have been mixed (Attal et al. 2000; Attal et al. 2002).

Post Traumatic Headaches (PTH)

Damage to the skull, brain tissue, or to the cervical spine can result in PTH and can be serious and incapacitating (Watanabe et al. 2012). According to Elkind (1989), headache is a common and dominant symptom of TBI, with approximately 44% of those who sustain a closed head injury developing PTH. Head, neck and shoulder pain usually begins within the first 24 to 48 hours post injury (Young 2001); PTH may appear immediately after the injury and subside, or occur days, weeks or months following the injury.  Factors that may lead to PTH include chronic muscle contraction, chronic and diffuse muscle strain and anxiety (Hillier et al. 1997). Visual or vestibular system complications may also result in headache syndromes. Studies have found that PTH often resolves itself within the first 6 to 12 months of injury; however, in 18-33% of the TBI population headaches persist longer than one year (Lew et al. 2006; Seifert & Evans 2010). Estimating the number of individuals who develop PTH is difficult as there is lack of consistency in how PTH is defined which may reflect limited understanding of its pathophysiology.

Previously, studies looking at the incidence of PTH reported that those who sustained a mild TBI were more likely to report problems with headaches than those who sustained moderate to severe TBIs (Couch & Bearss 2001; Gurr & Coetzer 2005; Uomoto & Esselman 1993). However, more recent studies have found that individuals with moderate or severe TBIs report experiencing headaches even at one year post TBI (Hoffman et al. 2011; Hoffman et al. 2007; Lainez & Pesquera 2011). In a survey of 485 individuals, Hoffman and colleagues (2011) found the prevalence of headaches during the first year of recovery post TBI was 40%, regardless of the severity of injury. Lucas (2011) found almost 60% of respondents who reported experiencing headaches, also reported experiencing migraines or probable migraines. Other headaches reported were tension type headaches, cervicogenic headaches or unclassifiable headaches. Despite what is known about PTH, there remains a need for further epidemiological, clinical and pathophysiological studies (Lainez & Pesquera 2011).

Non-Pharmacological Treatments for Pain and Post Traumatic Headache

Early detection of pain and treatment is regarded as crucial (Ivanhoe & Parrilla 2002) to ameliorate its impact and help individuals avoid developing maladaptive approaches to dealing with their pain. As mentioned previously, deciding on a treatment for both general pain and PTH may be a challenge due to the many underlying factors of TBI and the fact that some pain conditions are only partially responsive to treatment. Given that pharmacological interventions may worsen cognitive deficits post TBI, non-pharmacological interventions should be incorporated into the treatment plan.

Non-pharmacological interventions for both chronic pain and PTH may include: biofeedback, cold and heat packs, massage therapy, acupuncture, and exercise (Medina 1992). Biofeedback, relaxation, meditation and CBT are considered the gold standard of behavioural treatments for pain (Branca & Lake 2004). In a recent review of manual treatments for migraines, massage therapy, physiotherapy, relaxation and chiropractic spinal manipulative therapy were found to be just as effective as propranolol and topiramate (Cassidy et al. 2014). Physiotherapy exercises have also been suggested to treat pain; however, unless the pain is controlled, caution is recommended when using these exercises to prevent aggravating the painful structures further (Medina 1992). Lifestyle changes are also suggested to prevent the onset of PTH, such as getting enough sleep and daily exercise. 

Biofeedback to Manage Post Traumatic Headache

According to a study by Mullally et al. (2009) biofeedback therapy was not found to significantly reduce the number and severity of headaches in individuals who were diagnosed with migraines or tension type headaches. Several earlier studies found more positive results. A study by Ham and Packard (1996) studied 40 individuals who sustained a mild TBI and were experiencing post traumatic headaches. Subjects participated in biofeedback sessions and were placed on anti-depressants and anti-inflammatory or non-narcotic analgesics. Participants began treatment on average 12.7 months post injury, although in half of the participants PTH occurred immediately post injury. Biofeedback was reported to help 93% of participants to some degree. Those who waited longer to begin biofeedback therapy found it less successful. Those who had more sessions and began treatment sooner found the sessions to be very beneficial. Unfortunately, the research on this topic for the moderate to severe TBI population is limited.

Individual Studies

Table: Biofeedback and Post Traumatic Headache


In the study by Tatrow et al. (2003) PTH were targeted for six weeks in 14 individuals. The first four sessions consisted of progressive muscle relaxation, with biofeedback (Thermal and EMG) being introduced in the fifth session. As a result of the sessions participants learned to relax and control muscle tension. Relaxation ratings were on average 8.6 out of 10. Improvements in PTH were shown for the majority of participants. The treatment also lowered post-concussion syndrome checklist scores significantly in the treatment group (Tatrow et al. 2003).


There is Level 2 evidence from a single, small sampled cohort study suggesting that biofeedback is effective in the treatment of post traumatic headaches; although, the severity of the participants was not clearly stated.  


Despite the positive results of the study investigating biofeedback and post traumatic headaches, further research needs to be completed using larger groups and only with those who have moderate and severe TBIs.



Cognitive Behavioural Therapy

Cognitive behavioural therapy (CBT) has been used to assist individuals in managing their pain. It is considered a diverse set of problem–specific interventions (Roth & Pilling 2008) and incorporates physical, psychological and behavioural approaches to managing pain. With CBT the individual is taught to use self-regulation, self-control and to take responsibility for one’s lifestyle (Martelli 2012). This therapy has been used to help patients cope with the pain, depression, and anxiety associated with chronic headaches (Gurr & Coetzer 2005; Wetherell et al. 2011).

Wetherell et al. (2011) recruited 114 individuals for a RCT investigating the effects of acceptance and commitment therapy and CBT on chronic pain. Following randomization of the participants, those in the acceptance and commitment therapy group were taught to focus on changing their expectations from completely eliminating the pain to thoughts of living with it as best as possible. Those in the CBT group were taught to manage their pain by monitoring it, pacing, increasing pleasant activities, progressive muscle relaxation, etc. Both groups received eight 90 minute sessions. Both groups showed improvement on depression scores, pain related anxiety and pain interference; however, those receiving acceptance and commitment therapy reported greater levels of satisfaction overall.  

Individual Studies

Table: Cognitive Behavioural Therapy and Pain Management


Gurr and Coetzer (2005) studied twenty participants who had sustained a mild to severe TBI and who had completed a CBT program for PTH. The CBT program consisted of progressive muscle relations, psycho-education, cognitive behavioral strategies, lifestyle management and maintenance and relapse prevention. Headache intensity and the headache frequency significantly decreased. Headache disability also decreased, while emotional wellbeing increased. Results from the Nottingham Health Profile pain scale found no significant differences in pain pre and post intervention.


There is Level 4 evidence supporting the use of CBT to reduce post traumatic headaches in those who have sustained a mild to severe TBI.​


CBT has been found to be useful in managing post-traumatic headaches; however, the pain associated with these headaches was not decreased following treatment.



Relaxation Training

Relaxation training, or progressive muscle relaxation, is a possible treatment for chronic pain and PTH. Individuals are taught how to breathe from the diaphragm and how to tense and relax various muscles. Through such techniques, the muscle tension triggers associated with headaches can be better controlled (Arnstein 2004). Over time, patients are may be able to reduce the number of headaches or prevent the pain for worsening. 

Manual Therapy

Manual therapy refers to more hands-on types of therapy such as massage therapy, traction, mobilization and physical therapy. The purpose of these therapies is to reduce muscle tension, increase muscle length, enhance circulation and increase mobility in the joints (Gould 2007). The results from an earlier study indicated that manual therapy was more effective than cold packs in reducing pain associated with PTH (Jensen et al. 1990).

Massage therapy involves either deep tissue massage or a lighter massage technique. Massage therapy has been shown to increase oxygenation and blood flow to the muscles being treated. Overall, massage therapy has been shown to reduce pain (D'Arcy 2011). Physical therapy involves the patients and a physical therapist working together to identify the areas where pain is being experienced. Therapy may involve stretching and or strengthening exercises, ultra sound to the affected areas, or the application of hot and cold packs. Physical therapy for both pain and chronic daily headaches focuses on the upper body, including the upper back, neck, and face (Sherman et al. 2006).

In an earlier study, Medina (1992) investigated the treatment of PTH in 20 patients post TBI or spinal cord injury through individualized therapeutic sessions each lasting 30 minutes. Patients received education sessions, biofeedback training, electromyographic biofeedback, or physical therapy sessions and were placed on appropriate medication to treat the pain.  The combination therapies were effective with 17 patients returning to work and 19 patients reporting a decrease in PTH intensity. 


Physical therapy, stress management and biofeedback have been shown to reduce post-traumatic headaches in those who have sustained either a TBI or spinal cord injury, allowing individuals to return to work.




Acupuncture, one of the oldest forms of physical therapies, is a non-medicinal intervention involving a certified acupuncturist selecting particular points on the body to insert acupuncture needles. The points of insertion differ from every individual. Although the research indicates there is some benefit to acupuncture therapy, there is a lack of strong evidence supporting its effectiveness with the TBI population (Gould 2007; Wong et al. 2012). 

Cryotherapy and Thermotherapy

Heating and cooling therapy can provide relief to sufferers of chronic headaches and neck pain. Cryotherapy involves the application of cold to relieve pain. On the other hand, thermotherapy involves the application of heat to relieve pain (Pangarkar & Lee 2011). Both therapies are typically used in conjunction with other treatments.

Individual Study

Table: Cold Therapy to Treat Post Traumatic Headaches


Jensen et al. (1990) compared manual therapy to cold pack therapy for the treatment of PTH in 19 participants with head injury.  Those in the manual therapy group reported a significantly greater reduction in pain following the intervention when compared to the cold pack group. The pain index for all participants was also correlated with the frequency of associated symptoms (dizziness, visual disturbances and ear symptoms) and the use of analgesics. 


There is Level 2 evidence suggesting the use of cold packs is not as effective as manual therapy in reducing post traumatic headaches.


Cold therapy is less effective in reducing post traumatic headaches than manual therapy.


Pharmacological Management of Pain and PTH

There are a variety of medications used in the treatment of chronic pain post ABI and PTH. Aspirin or aspirin compounds, acetaminophen, and ibuprofen are often the first lines of treatment prescribed for chronic pain; however, adjuvant medications such as anticonvulsants, antidepressants, benzodiazepines, bisphosphonates, local anesthetics, antispasmodic agents and topical agents may also be prescribed (Gould 2007; Khan et al. 2011). In some cases the prescribing of opioids may be considered. 


The administration of anticonvulsants to treat pain post brain injury has been a common practice since the 1960’s. It is felt that epilepsy and pain share a common pathogenesis thus allowing anticonvulsant medications to be used in pain management, particularly neuropathic pain, either peripheral or central in origin (Dickinson et al. 2000; Zasler et al. 2011). It has also been noted that the use of anticonvulsant medication seems to produce fewer adverse events (Gould 2007). Anticonvulsants currently used to treat pain include carbamazepine, oxcarbamazepine, lamotrigine, gabapentin, pregabalin, and topiramate; however, there are limited studies investigating their effectiveness either in isolation or in combination with other medications.

Table: Antiepileptic Medications used to Treat Pain Post Traumatic Brain Injury (Gould 2007; Guay 2003; Zasler et al. 2011)

Antiepileptic Medication

Typical Dose; Dose Range

Adverse Events (partial list)

Carbamazepine (Tegretol®)

200 mg q 8h; 100-1600mg/d

Drowsiness, bone marrow suppression, kidney stones

Valproic acid (Depekene®)

250 mg q 8h; 600-2400 mg/d

Drowsiness, headache, sleepiness, agitation, mood swings, memory loss

Phenytoin (Dilantin®)

100 mg q 8h; 200-600mg/d

Double vision, imbalance, slurred speech

Gabapentine (Neurontin®)

600mg q 8h; 200-3600mg/d

Drowsiness, dizziness

Clonazepam (Klonopin®)

0.5mg q 8h; 2-7mg/d

Drowsiness, disequilibrium, abnormal behavior

Oxcarbazepine (Tripeptal®)

300-600 mg q 12h; 150-1800mg/d

Drowsiness, lightheadedness, dizziness

Lamotrigine (Lamictal®)

50-100 mg q 12h; 50-200mg/d

Rash, fatigue, stomach upset


25mg q 12h; 200-400 mg/d

Ataxia, impaired concentration, confusion, dizziness, fatigue, speech disturbances, language problems.

Pregabalin (Lyrica®)

300-450 mg/d; 150-600 mg/d

Drowsiness, dizziness

Levetiracetam (Keppra®)

250-500 mg q 12h; 250-1500mg/d

Drowsiness, dizziness


Valporic Acid and Divalproex Sodium

Valporic acid and divalproex sodium are antiepileptic medications that have been used to reduce pain; however, there are no clinical trials showing its efficacy post moderate to severe TBI. A retrospective study investigated the effectiveness of divalproex sodium on PTH in a mild TBI population. The dosing was individualized, with the starting dose was 250mg per day and was increased by 250mg as needed. Results showed that 60% of those on divalproex found mild to moderate improvement in chronic daily PTH. Further, 19 of 28 participants who had chronic daily headaches reported mild to moderate improvement. Six participants were headache free after a single month of treatment (Packard 2000). The authors suggest divalproex is effective as it works by activating the inhibitory neurotransmitter γ aminobutryic acid (GABA). Packard (2000) noted that although PTH that persist for more than one year are considered permanent, it is possible to treat them effectively, allowing the patient to increase their activity level and perhaps reduce their dependence on other analgesics. 


Divalproex has been found to improve post traumatic headaches in those who sustain a mild TBI.



Pregabalin and Gabapentin

Pregabalin and gabapentin work by blocking neuronal calcium channels and have become widely used for the treatment of neuropathic pain, in particular peripheral neuropathic pain. Gabapentin requires a longer time to reach a therapeutic dose; pregabalin, however, can provide a faster response to pain as it is 90% bioavailable. Pregabalin does not appear to have a negative effect on other medications that an individual may be taking (D'Arcy 2011; Vranken et al. 2011). Gabapentin has been found to be very effective in treatment of neuropathic pain in the elderly and is considered the first line of defense with this population (Guay 2003). Again, despite these medications being administered to individuals post TBI, there is little in the literature supporting their effectiveness in this population.

In a RCT by Vranken et al. (2008) the effects of pregabalin on pain in those with either an ABI or spinal cord injury were examined. The intervention group received a flexible dose of pregabalin, starting at 150mg per day. If the pain relief was insufficient, the dose of pregabalin was increased to 300mg, then 600mg if needed. The control group received a placebo. Participants were administered the medication or placebo twice a day over the span of four weeks. Results indicate those in the pregabalin group reported a significant decrease in pain intensity, measured by a VAS, compared to the control group (p<0.01). When using the Pain Disability Index, no significant between-group differences were noted at the end of the intervention. Of note, those in the pregabalin group reported few side effects indicating that the medication was well tolerated (Vranken et al. 2008). 


Pregabalin has been shown to reduce central neuropathic pain post ABI or spinal cord injury.



Carbamazepine and Oxcarbazepine

Oxcarbazepine has been found to be effective in the treatment of neuropathic pain (Nasreddine & Beydoun 2007). In patients experiencing painful diabetic neuropathy, oxcarbazepine resulted in decreased VAS pain scores; however, changes were not always statistically significant. When administered to patients with the pain of trigeminal neuralgia, oxcarbazepine was found to be effective in reducing pain (Nasreddine & Beydoun 2007). Overall, oxcarbazepine has been found to have an improved side effect profile compared to carbamazepine. Carbamazepine was once considered the drug of first choice for treating neuropathic pain (Gould 2007). Despite its success there has been considerable concern over the adverse effects many experience while on the medication. If administering carbamazepine the monitoring of such adverse events is strongly recommended (Backonja 2003).


Lamotrigine, a newer anticonvulsant medication, has also been found to aid in the treatment of neuropathic pain often associated with diabetic neuropathy, spinal cord injury pain, phantom limb pain, postoperative and traumatic neuropathic pain, and cancer related neuropathy (Ettinger & Argoff 2007; Wiffen et al. 2011).


Topiramate has been found to be successful in treating migraine and cluster headaches (Ettinger & Argoff 2007). Although topiramate is believed to be effective in treating pain, it has been noted that any preexisting cognitive impairments (language, attentions, cognitive functioning or memory) due to the brain injury itself may be exacerbated by topiramate (Tang et al. 2007). 


Among the antidepressant medications available, tricyclic antidepressants are the most commonly used for the treatment of pain, in particular neuropathic pain (Gironda et al. 2009; Gordon & Love 2004; Guindon et al. 2007). Medications such as fluoxetine, sertraline, paroxetine, or citalopram work best at controlling pain when there is an underlying primary problem such as depression. Tricyclic antidepressants used to treat pain include amitriptyline, nortriptyline, desipramine, doxepin and imipramine (Gould 2007); however, the mechanism of action for these medications in the treatment of pain is not yet fully understood. Currently there is no evidence to support the administration of antidepressants to treat pain or PTH. 

Table: Anti-depressants to Treat Pain Post Acquired Brain Injury (Gould 2007; Zasler et al. 2011)


Typical Dose; Dose Range

Adverse Events

Amitriptyline (Elavil®)

75mg qhs; 10-150 mg/d

Drowsiness, dry mouth, weight gain, constipation, seizures, cardiac toxicity, urinary retention

Venlafaxine (Effexor®)

37.5 mg od; 150-225mg/d

High blood pressure, weight loss, dry mouth, impotence, tremor

Nortriptyline (Pamelor®)

75mg qhs; 10-150 mg/d

Drowsiness, dry mouth, weight gain, constipation, seizures, cardiac toxicity, urinary retention

Desipramine (Norpramin®)

75mg qhs; 50-200 mg/d

Drowsiness, dry mouth, weight gain, constipation, seizures, cardiac toxicity, urinary retention

Duloxetine (Cymbalta®)

60mg qd; 3-120 mg/d

Insomnia, nausea, dizziness, fatigue, constipation

Fluoxetine (Prozac®)

20mg qd; 5-60mg/d

Anxiety, nervousness, insomnia, tremor, chest pain, diarrhea

Paroxetine (Paxil®)

20-40mg qd; 20-50 mg/d

Drowsiness, dizziness, insomnia, headache


Amitriptyline and Pain Post TBI

Amitriptyline is often used to treat headaches in those who suffer from migraines and has been found to be very effective (Pringsheim et al. 2012). Along with treating migraines, amitriptyline has been used to treat pain in patients since 1964 when its efficacy was first demonstrated (Adelman et al. 2000). It is used to treat pain in those who have suffered a stroke or spinal cord injury, and in those who have been diagnosed with dementia, multiple sclerosis, fibromyalgia, or chronic diabetic peripheral neuropathic pain. The effectiveness of amitriptyline in the treatment of pain post TBI is not well studied.

Venlafaxine and Pain Post TBI

Venlafaxine, a serotonin and norepinephrine reuptake inhibitor, has been shown to be a safe and effective medication in the treatment of depression and anxiety, as well as for various pain syndromes including, neuropathic pain, headaches, fibromyalgia, painful peripheral diabetic neuropathy and post mastectomy pain (Dharmshaktu et al. 2012). Venlafaxine, amitriptyline and propranolol are the most prescribed medications in the treatment of migraine related pain, and chronic tension type headaches (Adelman et al. 2000). 


Although antidepressants (i.e., Selective Serotonin Reuptake Inhibitors, tricyclic antidepressants) are often prescribed to treat pain, there is little evidence supporting this practice in general and no evidence supporting this post TBI.



Topical Analgesics

Pain that is described as localized and superficial has been treated very effectively with topical treatments. Topical analgesics include menthol/methylsalicylates, capsaicin and anesthetics; however, as with other medications there is no clinical evidence to support using these topical analgesics. Menthol has been shown to be somewhat effect as it releases a cooling sensation over the painful area (Pangarkar & Lee 2011). Capsaicin cream has been found to cause a burning sensation, so it is strongly recommended to apply the cream only to where the pain is located. Despite this, capsaicin cream has been found to decrease neck pain (Pangarkar & Lee 2011). The lidocaine patch is applied to the painful area and worn for typically 12 hours. The patch tends to be well tolerated by most (D'Arcy 2011). 

Table: Topical Anaesthetics Used to Treat Pain Post Traumatic Brain Injury (Gould 2007)


Typical Dose

Adverse Events

Capsaicin (Zostrix®, Axsain®)

0.025-0.075% 3-4 times daily

Burning, skin irritation

Lidocaine 5% (Lidoderm®)

1-4 patches 12hrs/d

Skin irritation



The use of opioids to manage non-cancer pain has been on the rise for the past several decades (Martelli 2012). It is believed that neuropathic pain can be relieved by the administration of opioids, provided a balance exists between the optimal dose and any unmanageable side-effects (Dellemijn 1999). A decrease in libido, sedation, mental dullness, difficulties concentrating, and a higher risk for developing osteoporosis have been reported when taking opioids (Ersek et al. 2004; Haanpaa et al. 2010). The risk of exacerbating cognitive impairments of patients with TBI is one of the reasons for clinicians’ hesitancy in using opioids for pain management. Although opioid use within a TBI population has been discussed in the literature, few studies investigate its efficacy within this population. When opioids are administered it has been suggested to start with a low dose and titrate up (Gallagher et al. 2006). Unfortunately with narcotics there is no recommended therapeutic dose (Khan et al. 2011); although with musculoskeletal complaints it is recommended that the dose not exceed 120-200 mg/day morphine equivalent dose (Haanpaa et al. 2010). Moreover, with opioids, because the risk of physical dependency and addiction is problematic, patients should be screened for addiction and dependency risk factors.  Psychological problems and a history of substance abuse are considered the two most common risk factors for opioid misuse and addiction.

Franceschi et al. (2008) administered oxycodone to a group of polytrauma patients, five of which has mild head injury, admitted to an emergency department suffering from acute pain. Main pain sites for the group were the chest, neck, lower back, leg, heel, pelvis, upper arm and shoulder. Oxycodone (10mg twice per day for three days given orally) was found to significantly reduce pain for 14 of the 15 patients. One patient required an increase in medication (20mg twice per day) to achieve pain relief. Overall the medication was well tolerated by patients with some reporting mild side effects (light headaches, constipation and nausea) (Franceschi et al. 2008).


Oxycodone in modest doses is effective in reducing pain following mild TBI.

Oxycodone has been found to be successful in reducing pain: however it remains unclear as to whether or not this medication would be effective and well tolerated in those who sustain a moderate or severe ABI. More research is needed.



Cannabinoids and Pain

Cannabis sativa has been used to treat pain for centuries; however, cannabis (and its derivatives) to treat pain had fallen out of favour in the mid 1940’s to the mid 1990’s, possibly due to the suspected risk of addiction, abuse, dependence, cognitive effects and other adverse medical and psychiatric effects (Aggarwal 2013; Greenwell 2012). The utility of the medication is gaining increasing recognition as physicians and other health care professionals increase their knowledge regarding the efficacy and safety of the cannabinoid based medications (Aggarwal 2013). Cannabis is generally administered through inhalation, ingestion or topically. The method of delivery determines the rate at which the drug begins to take effect. According to Aggarwal (2013) the use of cannabinoids can result in muscle relaxation, anti-inflammatory effects, neuroprotection in ischemia and hypoxia. Currently cannabinoids are used to treat cancer pain, pain associated with Multiple Sclerosis, Human Immunodeficiency Virus, fibromyalgia and rheumatoid arthritis. Although many studies have looked at the benefits of using cannabinoids to treat chronic pain, the results of many of these studies was inconclusive (Greenwell 2012).

A study by Ware et al. (2010) examined the effects of cannabis at different potencies (0%, 2.5%, 6% and 9.4%) to individuals with post-traumatic or postsurgical neuropathic pain. Pain intensity was found to be significantly lower on 9.4% tetrahydrocannabinol cannabis than on 0% tetrahydrocannabinol (p=0.023).  Further, when 9.4% tetrahydrocannabinol cannabis was compared to taking a placebo, patients experience more drowsiness and fewer periods of wakefulness. Results from Ware et al. (2010) suggest cannabis is effective in the treatment of neuropathic pain. Due to the addictive properties of this group, cannabinoids should only be administered if there is no history of alcohol or drug addiction. Once on these medications monitoring of patients is paramount.

Although pain is a frequent problem post TBI there is little in the literature on how best to manage and treat pain. More research is needed to assess the effectiveness and efficacy of these treatments with the TBI population. For a summary of these findings please see Diagram 1.


Cannabinoids have been shown to reduce post-traumatic and postsurgical neuropathic pain. More studies are needed investigating its effectiveness in treating pain post TBI.