Medications for Chronic Pain

Considering Medications in Physiotherapy and Pain Management

Timofei Alekseevich Dovbysh

Final Year Physiotherapy 2010

University of  Otago

School of Physiotherapy

New Zealand

 

This research document was prepared as part of a final year placement assignment, and is supplied with the author’s permission.

It is to be used for information purposes only.

Please discuss your medication needs and use with your regular medical provider.

 

INTRODUCTION

BurwoodHospital is home to the Pain Management Centre (PMC). The PMC is a tertiary referral centre that receives referrals from general medical practitioners, specialists and private insurer case managers. At the PMC an interdisciplinary approach is employed to provide assessment and intervention for individuals with chronic pain. The purpose of the PMC is to encourage a return of function and independence to individuals whose reduction in activity is influenced by their pain.

The intervention of pain management focuses on teaching self management techniques regarding living with pain rather than looking for a cure. A bio-psychosocial model is used in place of the traditional bio-medical model where patient care is guided by physiotherapists, medical and psychosocial team members.

For the model to be effective, the three professions must provide a complementary intervention. To enable this, it is vital that there is an understanding of which approach each team member takes.

The purpose of this report is to raise some awareness about the medications prescribed by the PMC medical clinicians and how this use can relate to physiotherapy practice at the PMC and in other clinical settings.

 PAIN PATHWAYS

To understand how the pain is targeted with medication, we must first appreciate the possible pathways of pain. Woolf (2004) presents a model describing four varying pain pathways. These are nociceptive, inflammatory, neuropathic and functional. Each type of pain is controlled by a different neurological mechanism.

Nociceptive Pain

Nociception is perception of intense, noxious stimuli. The signals travel via an unmyelinated C-fibre or thinly myelinated A-delta fibres. The nociceptive receptors are activated by input of an intense temperature, chemical irritant or mechanical force. If the input is sufficient enough, the cell will depolarise initiating an action potential. The intensity and duration of the action potential corresponds to the frequency and duration of the stimuli. When this action potential reaches the brain, the signal is interpreted taking into consideration beliefs and context, and the output of pain is felt. This pain serves as an early warning device, alarming the brain when a potentially damaging stimulus is present. It serves a protective function, signalling to reduce exposure to harmful stimuli when working properly (Woolf, 2004).

Inflammatory Pain

If the protective nociceptive pain pathway  fails to prevent tissue damage, the body’s priority changes from protecting against the stimuli to repairing the now damaged tissue. This is the role of inflammation, and the introduction of inflammatory pain. The body undergoes changes for the purpose of promoting healing of the damaged tissue and the pain is mediated by inflammatory chemicals. These irritants can be a source of pain. Sensitivity to a stimulus can increase around the affected area, causing pain in situations that would previously be pain-free. If via a reduced threshold it is called allodynia: if as an increased response, it is hyperalgesia. Our reflex is to prevent contact or movement of that injured part to avoid pain, allowing for an environment where further damage is prevented and tissue repair can complete. In this pathway, as damage and inflammation resolve, the pain will decrease.

(Woolf, 2004)

Neuropathic Pain

This pathway of pain results from damage to the nervous system. It can occur via lesions to the peripheral nervous system as in diabetic neuropathy, or by damage to the central nervous system as in spinal cord injury, multiple sclerosis or stroke (Woolf, 2004).

Functional Pain

This pain pathway is an evolving concept. Here, no clear neurological or peripheral abnormalities are visible. The pain occurs due to a response or function in the nervous system that is abnormal. Conditions that can be placed into this category show an increased sensitivity to sensory input (Woolf, 2004).

Adaptive Pain

Woolf (2004) continues to present this model of pain by grouping the four pathways into two categories. One group he calls adaptive pain, and the pathways that fall into this category are nociceptive and inflammatory pain. The goal of intervention at this level is to normalise the pain, not to remove it. The purpose of these pain pathways is as a protective mechanism, helping to avoid tissue damage or to encourage healing.

The pain pathways that appear here are commonly attributed to acute pain, and are managed from a pharmacological perspective with simple analgesics or non-steroidal anti-inflammatory drugs (NSAIDS)

 Maladaptive Pain

This category includes the remaining neuropathic and functional pain pathways. Where adaptive pain can serve a purpose, maladaptive pain has no function and is a pathological process on the nervous system. It is this category of pain that presents in the patients that are referred to Pain Management Clinics , and the PMC (Woolf, 2004).

MEDICATIONS IN CHRONIC PAIN

 In an acute setting, the type of pain most commonly experienced is nociceptive and inflammatory. In these settings, simple analgesics and NSAIDS are used suitably (Ashbum and Staats, 1999). However, this is not the typical course of action for chronic pain, or the type of pain that is seen at Pain Management Clinics. The commonly used medications for chronic pain (neuropathic and functional) at the PMC are not traditional analgesic drugs. They are antidepressants, anticonvulsants and to some degree, opioids. The following will provide an overview into how those drug classes are used to target pain to provide an analgesic effect.

 ANTIDEPRESSANTS

The analgesic mechanisms by which antidepressants work are unclear, but it is almost certain that it is independent from their antidepressant effect. There is controversy surrounding whether the antidepressant effects are separate from analgesic effects, but reports in a systemic review by McQuay et al (1996) show analgesic benefit without mood alteration. Another reason for independent effects is shown as the dosage at which analgesic effects occur, are far below the effective dosage for the antidepressant effect.

Within this drug class are three families that are used. Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are the traditional families of choice. A newer family- serotonin-norepinephrine reuptake inhibitors (SNRIs) has recently been introduced. TCAs are the oldest of the three and are routinely used as a therapy in neuropathic chronic pain.

The multiple analgesic mechanisms remain unclear but are believed to work centrally at the dorsal horn, by enhancing the endogenous pain inhibiting pathway (Mico et al, 2006). This effect is achieved through inhibition of reuptake of serotonin and norepinephrine at the presynaptic membranes, resulting in an increased nociceptive threshold (Sundrup et al, 2005). For peripheral analgesia, it is possible that there is influence on the blocking of histamine receptors and binding to opioid receptors. As well as these proposed mechanisms, antidepressants also exhibit action on cholinergic and N-methyl-D-aspartic (NMDA) receptors and on ion channel inhibition (Mattia and Coluzzi, 2005).

Where TCAs are believed to work on serotonin and norepinephrine, SSRIs only work on serotonin. Coincidentally, there is better evidence for the efficacy of TCAs than there is for SSRIs (Lynch, 2001). A systematic review by McQuay et al (1996) reports SSRIs are less effective than TCAs but have half the major adverse side effects. The newest family of antidepressants are the SNRIs. They work similarly to TCAs in that they also inhibit serotonin and norepinephrine reuptake, but have fewer side effects. They have the fewest published studies of the three as they are the newest drug.

Anticonvulsants

Traditionally, this drug class has been used in the management of epilepsy. A Cochrane review by Wiffen et al (2009) looked at evaluating the analgesic effects of anticonvulsants for managing pain in a clinical environment. The authors conclude that there is no evidence for analgesic effects of anticonvulsants for acute pain, but for chronic pain the results were more promising.

These drugs have also not traditionally been associated with pain management but have been shown to be effective in a range of neuropathic conditions (Ashbum and Staats, 1999). Their mechanism of action in chronic pain remains unclear but may act by stabilising  sodium channels. It is hypothesised that this may reduce the ectopic firing in nerones within the CNS that process nociceptive signals. However, evidence for this in the commonly used drug gabapentin is weak (Bennett and Simpson, 2004).

Another proposed mechanism is believed to be the action and enhancement of gamma-aminobutyric acid (GABA) inhibition. These two mechanisms are believed to be the standard, but another proposed mechanism argues that the analgesic action occurs via the N-methyl-D-aspartate (NMDA) receptor sites. Newer evidence into the commonly used gabapentin suggests there is binding to presynaptic voltage gated calcium channels in the dorsal horn, resulting in decreased release of excitatory neurotransmitters like glutamate, substance P and norepinephrine (Dworkin et al, 2007). Like most drugs, anticonvulsants are not without risks and side effects. The most common adverse effects of this drug class include impaired motor and mental function

Opioids

Opioids produce an analgesic effect by binding to opioid receptors in the Central Nervous System (CNS). Evidence for the use of opioids in chronic pain is controversial. It was initially reported that opioids did not support an analgesic effect in neuropathic pain. Further studies then suggested that there was a lack of evidence to support this claim. But more recent reviews have reported there are some neuropathic pain states that do respond to opioid therapy. However, this effect is not universal as there are too many variations in the pathophysiology of neuropathic  pain states between individuals and it has been suggested that neuropathic pain is less sensitive to opioids.

Given the inconsistency in evidence, opioids have been identified as a second or third line drug in neuropathic pain management ((Ballantyne and Mao, 2003)  (Dickenson, Matthews and Suzuki, 2002).

CLINICAL APPLICATION OF MEDICATIONS IN CHRONIC PAIN

A recent review by Freynhagen and Bennett (2009) looked to establish a recommendation for the sequence of drugs to use in a neuropathic pain presentation. The authors identified that the first line treatment are TCAs. This is partly due to the abundance of well supported evidence for their use. At the PMC TCAs which are commonly prescribed are amitryptiline and nortryptiline. SNRIs reported as being first or second line drugs. However, it must be noted that this family of antidepressant is relatively new so would not have been involved in as many trials as TCAs.

Due to the safer nature of SNRIs compared to TCAs, it is possible that with time and more research they will overtake TCAs as the drug of choice. Coincidentally, these two members include norepinephrine as a mechanism of action whereas the SSRIs such as citalopram only act on serotonin and are third line drugs.

The report identifies anticonvulsants as another first line drug of choice for neuropathic pain. Pregabalin and gabapentin are also both frequently prescribed at PMC.

Opioids appear as second or third line approaches. Along with the controversy and conflicting evidence previously mentioned surrounding their use in chronic pain, there are potential safety concerns involving tolerance, addiction and cognitive impairment , and hence they are recommended as second or third line treatments.

 CLINICAL IMPLCATIONS OF MEDICATIONS IN PHYSIOTHERAPY

As described in the introduction, the PMC follows a bio-psychosocial model where there is input from members of the medical, psychosocial and physiotherapy team in patient care. For effective intervention it is beneficial to be aware of the approaches the individual team members are employing, so as to channel intervention into one global goal. At PMC the psychosocial team  employ Cognitive Behavioural Therapy and provide education on pain management strategies. The medical team provide medical information and may prescribe relevant medications or referral for further medical intervention if deemed necessary.

Having knowledge about the medications that are being prescribed allows the physiotherapist to have greater insight into the patient’s treatment. If, for example, the patient  has recently been prescribed a NSAID, we could surmise that there is an inflammatory process occurring that is being controlled, hence we can proceed with techniques that could otherwise be contraindicated due to acute inflammation. This would not only be applicable to the PMC but would have cross over into musculoskeletal, cardio / respiratory or neurological fields.

Many patients that attend the PMC have a strong biomedical focus surrounding their condition. Being aware of the effects and purpose of the medications that they are currently prescribed can allow for a brief discussion into any patient generated questions regarding their medications. It is possible that a patient may question why they are being prescribed antidepressants when they are not depressed, or anticonvulsants when they do not suffer from epilepsy. Having an understanding that these drugs may be used for their analgesic effects means we can communicate this idea if confronted by it, helping building confidence within the patient.

Another possible patient generated question can be simply “why do I get my pain?”. It may be possible to answer this by gaining an understanding from their referral to the service, but as they present with chronic pain, we could explain why previous therapies may have failed to work, to help to give them a better understanding as to why they have been referred to the PMC.

It is possible that some practitioners work within the acute pain model framework, prescribing pharmaceutical management that would be appropriate for acute pain. If so, we could explain why with their chronic condition the previous intervention has failed, and why a new approach has been implemented.

When asking a patient about their prescribed medications, we ask about the drug class and also the pattern of consumption. Knowing the way the patient takes their medication gives us insight into how they are managing their pain. If it is being used in a pain-contingent approach, the patient is at risk of reducing function and becoming controlled by pain. During assessment the opportunity arises to inform the patient about the possible reduced benefit of taking medications in this manner and how a time-contingent approach would be more appropriate. Other team members would be addressing this issue too, so being able to apply the received information will benefit the patient , as a common theme will be voiced by the entire team, highlighting its importance to the patient.

Another aspect of medications that we can consider in our practice is monitoring the patient for side effects. An understanding of common side effects combined with regular appointments with the patient provides an opportunity to potentially monitor the effects of medications. As the physiotherapist sees the patient regularly, it may be the physiotherapist who begins to notice adverse reactions occurring and may be the one to alert the patient’s medical practitioner.

Conversely, we may find the patient is reporting decreased levels of pain but is becoming more deactivated as side effects affecting motor or physical function appear. Knowing that this may be due to their medications would indicate the need to discuss their outcomes and whether they are based on pain reduction or more in line with the ethos of PMC – ie, regaining function.

CONCLUSION

 Pain is a multidimensional output from signals received via various pathways. Acute pain follows the nociceptive and inflammatory paths. The patients attending the pMC usually present with neuropathic or functional pain. Pain in this setting is managed primarily with drugs not considered to be traditional analgesics, but have been found to have this effect. As medical management is part of the overall treatment it is beneficial to have an understanding of the rationale for these medications, as this can influence our interaction and intervention plan with the patient.

This knowledge is not only appropriate for the PMC but can cross over within other physiotherapy settings. Having this tool adds a dimension of clinical reasoning to your action plan.

REFERENCES

Ashbum, M. A., & Staats, P. S. (1999). Management of chronic pain. The Lancet , 353, 1865-1869.

Ballantyne, J. C., & Mao, M. D. (2003). Opioid therapy for chronic pain. The New England Journal of Medicine, 349, 1943-1953.

Bennett, M. I., & Simpson, K. H. (2004). Gabapentin in the treatment of neuropathic pain. Palliative Medicine, 18, 5-11.

Dickenson, A. H., Matthews, E. A., & Suzuki, R. (2002). Neurobiology of neuropathic pain: Mode of action of anticonvulsants. European Journal of Pain, 6, 51-60.

Dworkin, R. H., O’Connor, A. B., Backonja, M., Farrar, J. T., Finnerup, N. B., Jensen, T. S., Kalso, E. A., et al. (2007). Pharmacological management of neuropathic pain: Evidence-based recommendations. Pain, 132, 237-251.

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McQuay, H.J., Tramer, M., Nye, B. A., Carroll, D., Wiffen, P.J., & Moore, R. A. (1996). A systematic review of antidepressants in neuropathic pain. Pain, 68, 217-227.

Mico, J. A., Ardid, D., Berrocoso, E., & Eschlier, A. (2006). Antidepressants and pain. TRENDS in Pharmacological Sciences, 27 (7), 348-364.

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Wiffen, P. J., Collins, S., McQuay, H. J., Carroll, D., Jadad, A., & Moore, R. A. (2009). Anticonvulsant drugs for acute and chronic pain (review). The Cochrane Library,4, 1-33.

Woolf, C. (2004). Pain: Moving from symptom control toward mechanism-specific pharacological management. Annals of internal medicine , 140 (6), 441-451