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Long-term high-dose oral morphine in phantom limb pain introduction Long-term high-dose oral morphine in phantom limb pain introduction
Long-term high-dose oral morphine in phantom limb pain introduction Long-term high-dose oral morphine in phantom limb pain introduction

A 72-year-old man presented to the hospital complaining of radiating intense clutching pain, with occasional pins and needle sensations and heaviness in the missing limb. Thirteen years ago, he was diagnosed with malignant mesenchymal tumor of the upper one-third of the right tibia. The disease was localized with the absence of any surrounding metastasis. He had his right leg removed (above the knee). Postoperative pain was treated with epidural morphine (3 mg) bid for five days after the amputation, and the patient was completely relieved of pain. On discharge, the patient was prescribed paracetamol 1000 mg every six hours, oral morphine 5 mg every four hours and Bisacodyl 10 mg at bedtime. After seven days of discharge, the patient experienced pain in the missing limb.

 

The most likely diagnosis of this presentation is:

  • Phantom pain
  • Cancer


Chronic phantom limb pain (PLP) refers to the neuropathic pain affecting missing/ amputated limb. Phantom limb pain is common in all amputees with the incidence varying from 49% to 88%. Although the underlying pathophysiology of PLP is unclear, peripheral, spinal and central mechanisms are considered to play a significant role in pain modulation in amputees. Previous findings have indicated that the amputation of the lower limb could alter the cortical representation of the missing limb and the underlying white matter connections. The numerous treatment options for PLP include pharmacological agents like NSAIDs, opioids, antiepileptics and antidepressants. Research has suggested the use of opioids in treating neuropathic pain. Opioids may promote cortical reorganization in PLP patients. The effect of opioid is dose-dependent and prescribing high dose for treating PLP remains the point of interest.

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Key take away

Cancer patient after right above knee amputation developed phantom limb pain. The patient was given oral high dose morphine. The patient was relieved with no significant signs of addiction.

Examination & lab investigations

A general physical examination and the typical signs were suggestive of chronic phantom limb pain (PLP). The VAS score of the patient was found to be 8.

Management

The treatment of PLP was started with oral morphine 10 mg/ four hours, and the dose was gradually titrated to 120 mg/ four hours over four weeks. After this treatment, the VAS score was 1-2, suggesting an improvement in pain. He was asked to visit the hospital at least once in a month for the next 12 months, and the oral dose of morphine was continued. This stable dose of morphine offered 80-90% relief, and 1-3 VAS score was noted. However, in a later visit, the patient complained of more intense pain, and thus the dose of morphine was increased to 300 mg/ four hours. During the subsequent follow-up, there was no significant improvement in the pain. Therefore, epidural analgesia with 0.125% bupivacaine infusion was given, which effectively relieved the patient’s pain. Also, he did not experience any phantom sensations. Rebound pain and opioid withdrawal symptoms were observed if any attempt to discontinue oral morphine was made. Chemical lumbar sympathectomy was then started under fluoroscopic support at the level of L2 with 4 ml of phenol. After this procedure, the patient’s pain was partially relieved. A dose of morphine was gradually reduced to 240 mg/ four hours and the additional modalities like spinal cord stimulator, neuromodulator, and nerve blocks were undertaken as an additional treatment measure for the next few years. The dose of morphine was increased to 540 mg/ four hour due to inadequate pain relief and VAS score of >4. To avoid drug addiction with a high dose of morphine, the dose of morphine was gradually withdrawn that caused rebound pain, but there were no signs of addiction. Rorschach inkblot test, verbal adult intelligence scale (VAIS), Draw a person test, and Bender-Gestalt test was conducted to rule out the drug-seeking potential of the patient. The patient was found to have average intelligence with cluster B and C characteristics. The patient was discharged and prescribed 540 mg of oral morphine every four hours. Presently, he is in a good state of mind and has an active lifestyle.

Discussion

There is a lack of data reporting the maximum effective dose for treating chronic cancer pain. Dose titration is carried out to achieve optimal pain relief and to manage side effects. Previous studies have reported the need for high-dose morphine for treating PLP patients. In the present case, the patient required progressive dose increment as he experienced continuous phantom pain. Patients with neuropathic pain fail to achieve satisfactory pain relief with chemical sympathectomy and local epidural anesthetics. That is why a patient in the present case was given high morphine dose, which can be considered as the optimal dose for PLP patients. 

The need for high dose morphine may attribute to addiction potential or opioid-induced hyperalgesia. Addiction is a complex phenomenon characterized by carving and inability to control the consumption of drug despite severe consequences. The incidence of addiction in cancer patients receiving opioids has been found to be less than 1 per cent. The patient in the present case was found negative for addiction potential as per psychiatric evaluation. From the past seven years, the patient was stable on morphine dose without any prominent signs of addiction.

Opioid-induced hyperalgesia (OIH) may develop in the patients receiving opioids. It may cause a similar or different type of pain. OIH can be expected when patients experience an increase in pain intensity with increasing opioid dose. The patient in the present case did not show any signs of OIH.

Learning

Detailed pain estimation, along with analgesic titration, plays a critical role in the management of cancer pain. Morphine at high doses, when prescribed under supervision with regular assessment of pain and dose titration, does not show any addiction potential in PLP patients.

References

    1. Croci D, Fandino J, Marbacher S. Phantom Radiculopathy: Case Report and Review of the Literature. World Neurosurg. 2016 Feb 9. pii: S1878-8750(16)00217-5.
    2. Kumar V, Garg R, Bharati SJ, Gupta N, Bhatanagar S, Mishra S, et al. Long-term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk. Indian J Palliat Care. 2015 Jan-Apr;21(1):85-7.
    3. Lee JH, Byun JH, Choe YR, et al. Successful Treatment of Phantom Limb Pain by 1 Hz Repetitive Transcranial Magnetic Stimulation Over Affected Supplementary Motor Complex: A Case Report. Ann Rehabil Med. 2015 Aug;39(4):630-3.
    4. Jin QQ, Tang DD, Peng WW, Hu L. [The Research Advances of the Pathomechanism of Phantom Limb Pain (PLP)]. Sheng Li Ke Xue Jin Zhan. 2015 Oct;46(5):341-6.
    5. Jiang G, Yin X, Li C, et al. The Plasticity of Brain Gray Matter and White Matter following Lower Limb Amputation. Neural Plast. 2015;2015:823185.
    6. Raffin E, Richard N, Giraux P, Reilly KT. Primary motor cortex changes after amputation correlate with phantom limb pain and the ability to move thephantom limb. Neuroimage. 2016 Feb 11;130:134-144.

Source:

Indian J Palliat Care. 2015 Jan-Apr; 21(1): 85–87.

Article:

Long-Term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk

Authors:

Vinod Kumar et al.

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