Alternative medication for severe non-cancer chronic pain

There have been many questions about different options other than narcotics for severe non-cancer chronic pain. I try to address this question as complete as I can in the following paragraphs:

•  Around 1970, anesthesiologists started realizing that using many different medications with overall lower dose is safer than using one medication with high dose. Until then, the best anesthesia was “sole agent” and not “salad therapy”. We started understanding the pharmacology of the different families of medications, including benzodiazepines, narcotics, muscle relaxants and inhalation agents. 
  

• We started understanding the safety and efficacy of each agent and depend of the goal during the operation; we learned to use a specific medication. For instance an operation on the nose does not need muscle relaxation, so there is no need to use it.
  

• The concept of multimodal analgesia came to play in 21th century. We learned that using only morphine for post-op pain after total knee replacement is not enough. You have to use a very high dose that would reduce the safety of the patient as well as his/her ability to start physiotherapy as soon as possible.
  

•  We learned that adding one or two and even three medications, could provide a better result while it reduces the risk. Now-a-day, routinely acetaminophen and a NSAIDs and gabapentin use before operation and following the operation. The after operation meds includes morphine-kind of medication as well. We learned that there are 2 different kinds of pain:
  

• Resting pain- the pain that happens when patient does not move at all. This pain responds to morphine-like medications
  

• Active pain- the pain the feels when person starts moving for ambulation or physiotherapy. Morphine-like medications do not help this pain. Agents like gabapentin or NSAIDs would help more.
  

•  Three years ago, the first molecule that has multi-target action, Nucynta, came to market in Canada. This is the first narcotic after 20 years. Unlike other ones, Nucynta has ability to block Mu receptors (target for morphine-like medications) and inhibits norepinephrine reuptake in the neurons.
  

• Answering the main question, Nucynta is a very good alternative to morphine-like medications. Because of a different action, in a study over 2 years, as soon as the therapist found the right dose of medication, the dose did not increase over 2 years.
  

• Another very exciting replacement is Ketamine. Even the IV form could be absorbed from GI system. The main issue would be difficulty accessing the IV form, breaking the glass ampule or taking medication out of vials and extremely bad taste of Ketamine.
  

• Three years ago I thought about a different format, PO capsules. I asked a compound pharmacist and he agreed to make that for a few patients. In this form, Ketamine powder would be inserted into a capsule. Therefore the patient would not feel the taste.  It is a fairly old medication and the safety had been shown over years. The downside was the cost and the fact that patients need to take 3 doses a day. 
  

• There is no DIN number, so you cannot claim it to your insurance. For the minimum dose, the cost was over $100 per month. Fortunately I found a different pharmacy who is interested helping pain patients. She is willing to provide the same medication for about $50. Now it is a more acceptable option.
  

• Unfortunately we do not have lidocaine that can be absorbed by GI system; otherwise it would have been an amazing medication. Fortunately we have found a vehicle that can transfer lidocaine even over a healthy skin, PLO gel. Now I could add lidocaine and a few other medications to this gel and when applies topically, it would be effective. This is a very good alternative for pain in one small region.
  

• Adding meditation and stretch and exercise to Morphine-like medication, has an additive effect and therefore, can reduce the intake of those medications.
  

• Adding Cymbalta, a Serotonin–norepinephrine reuptake inhibitor, is very effective as addition and somehow effective as the sole medication. The anti-depressant effect of this medication, made it more attractive.
  

• Gabapentin, a GABA receptor agonist, was first studied as an antiepileptic drug in humans in 1987 (Crawford et al 1987). Even though it is structurally similar to GABA, gabapentin does not act through mechanisms related to this neurotransmitter.
  

• Gabapentin does not appear to affect the same pathways as opioid or tricyclic antidepressants. Current evidence indicates that it affects a voltage-gated calcium channel in the pain-transmitting nerve cells of the spinal cord. 
  

• In a very well done study; published by a friend of mine, Dr. Ian Gilron M.D. from Queen’s university, it has been shown that adding gabapentin to morphine was more effective that morphine alone. Pain Res Manag. 2009 May-Jun;14(3):217-22. Abstract 
  

  http://www.cbc.ca/news/health/story/2009/09/29/chronic-pain-neuropathic-drugs.html

• Tricyclic antidepressants had been used for a long time to treat depression. Now we just using them to control the pain. For Neuropathic pain, NNT(number of patients need to be treated that one of them feels meaningful relief) of these medication is lower than every other medication. (2.1) it means every 2 patient with neuropathic pain who be treated with this medication, one would feel a meaningful relief. NNT for lyrica is about 4 and for Cymbalta is about 7! 
  

o   You may wonder why you don’t see their advertisement on TV, if they are more effective. One reason is the cost. These medications are old; their price is so low that the manufacturers do not have much of profit and therefore no advertisement!