Opioid Induced Hyperalgesia: Clinical Implications for the Pain Practitioner

[Justin]

This is a great publication about opioids in the treatment of chronic pain. It spells out tolerance vs. pain sensitization among many other topics under the umbrella of opioid induced hyperalgesia. Here's a snip from the full-text:

Since tolerance is characterized by decreasing efficacy of a drug, it can be overcome by increasing the dose. However, unlike tolerance, OIH cannot be overcome by increasing dosage since OIH is a form of pain sensitization induced by the drug which occurs within the central nerve system (CNS) . Pain is worsened with increased opioid dosing and is improved by reducing or eliminating the opioid. Tolerance is a necessary condition for OIH, but the converse is not true. Clinically this is an important distinction that has obvious ramifications with respect to continued use of opioids in a given patient.

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Pain Physician 2009; 12:679-684 (May/June 2009 - Vol 12 Issue 3)

Opioid Induced Hyperalgesia: Clinical Implications for the Pain Practitioner

Sanford Silverman, MD

Opioids have been and continue to be used for the treatment of chronic pain. Evidence supports the notion that opioids can be safely administered in patients with chronic pain without the development of addiction or chemical dependency. However, over the past several years, concerns have arisen with respect to administration of opioids for the treatment of chronic pain, particularly non-cancer pain. Many of these involve legal issues with respect to diversion and prescription opioid abuse. Amongst these, opioid induced hyperalgesia (OIH) is becoming more prevalent as the population receiving opioids for chronic pain increases.

OIH is a recognized complication of opioid therapy. It is a pro-nocioceptive process which is related to, but different from, tolerance. This focused review will elaborate on the neurobiological mechanisms of OIH as well as summarize the pre-clinical and clinical studies supporting the existence of OIH. In particular, the role of the excitatory neurotransmitter, N-methyl-D-aspartate appears to play a central, but not the only, role in OIH. Other mechanisms of OIH include the role of spinal dynorphins and descending facilitation from the rostral ventromedial medulla. The links between pain, tolerance, and OIH will be discussed with respect to their common neurobiology.

Practical considerations for diagnosis and treatment for OIH will be discussed. It is crucial for the pain specialist to differentiate amongst clinically worsening pain, tolerance, and OIH since the treatment of these conditions differ. Tolerance is a necessary condition for OIH but the converse is not necessarily true.

Office-based detoxification, reduction of opioid dose, opioid rotation, and the use of specific NMDA receptor antagonists are all viable treatment options for OIH. The role of sublingual buprenorphine appears to be an attractive, simple option for the treatment of OIH and is particularly advantageous for a busy interventional pain practice.

Key words: Opioid hyperalgesia, hyperalgesia, tolerance, NMDA receptor antagonists, NMDA receptor induced hyperalgesia, spinal dynorphin induced hyperalgesia, descending facilitation and hyperalgesia, buprenorphine and hyperalgesia, opioid detoxification, office-based detoxification, complications of opioid therapy

See the FREE 6-page full-text publication that is attached.

[Justin]

Great publications on opioid-induced hyperalgesia... search PubMed for Jianren Mao here: PubMed.

Jianren Mao, MD, PhD is director, Massachusetts General Hospital Center for Translational Pain Research, and associate professor, Harvard Medical School, Boston, MA.

[muddywaters]

Thanks for this!

I have developed tolerance to Avinza at a scary rate. (Started at 30 mg, now up to 90 mg and need breakthru meds.

Am seeing a new PM doc tomorrow and fear he will taper me b/c of the pain.

I don't understand the literature re: biochem, etc. but are researchers certain that tolerance = hyperalgesia?

Also, should I expect tolerance to give way to global pain or pain in other areas as a given?

My concern about suboxone is what does one do for breakthrough pain.

Learning...

Thanks.

m

[Justin]

Thanks for this!

I have developed tolerance to Avinza at a scary rate. (Started at 30 mg, now up to 90 mg and need breakthru meds.

Am seeing a new PM doc tomorrow and fear he will taper me b/c of the pain.

I don't understand the literature re: biochem, etc. but are researchers certain that tolerance = hyperalgesia?

Also, should I expect tolerance to give way to global pain or pain in other areas as a given?

My concern about suboxone is what does one do for breakthrough pain.

Learning...

Thanks.

m

Hi Muddy,

Good luck with your new pain management doctor tomorrow. Tolerance =/= hyperalgesia. The are, in fact, different. Tolerance is requiring an increase in medication to achieve the same effect. Hyperalgesia is becoming hypersensitive to painful stimuli. Tolerance shouldn't cause global pain or pain in other areas; this would be more likely a manifestation of hyperalgesia in which nociceptive c fibers become extremely sensitive.

Suboxone was an incredible medication while I was on it. The coverage of pain with Suboxone was the best I've ever had. Personally, I don't think you would need anything for breakthrough pain.

[muddywaters]

Hi Justin!

Apologies for my late response and I wrote an idiotic post elsewhere that I should delete; unfortunately, I must run and am dumber from Neurontin.

Excellent link and response - thank you.,

OK, there is nocieptic pain and I forget the other type of pain fibers. *Proprioceptive*"? I must look this up!

Both you and Terry believe that Subxone is an excellent drug. Forgive the scepticism but on Avinza and Neurontin, I have pain that *needs* a strong breakthrough med (especially for a tooth needing a root canal!). This is my main concern and secondarily, that I've been told by one substance abuse "expert" that Suboxone is very hard to wean from. But I doubt I'd need that as a multi-level fusion, for reasons I don't understand, do nothing for discogenic back pain that for me is a nonstop drill-bit.

I have another question that links with receptors. Thank you again and apologies for my late response. I've been down and "in hiding".

Chow/my best of course ~ ans

Hi Muddy,

Good luck with your new pain management doctor tomorrow. Tolerance =/= hyperalgesia. The are, in fact, different. Tolerance is requiring an increase in medication to achieve the same effect. Hyperalgesia is becoming hypersensitive to painful stimuli. Tolerance shouldn't cause global pain or pain in other areas; this would be more likely a manifestation of hyperalgesia in which nociceptive c fibers become extremely sensitive.

Suboxone was an incredible medication while I was on it. The coverage of pain with Suboxone was the best I've ever had. Personally, I don't think you would need anything for breakthrough pain.

[KBear]

This is similar to what my pain doc said was happening with me. Of course, at first, I thought he was full of crap. I had pain, I felt pain and thought he just thought I was a druggie. Once I decided that I had had enough of the drugs and pain and was ready for a change, then I decided to test his 'theory'. Basically, he said that I was feeling pain, but it was being intensified by the drugs. I would however, get relief from opiods. But, I have found that my overall pain is way less without the opiods. I have also noticed, that when I do take a Vicodin for pain, I hurt more for the next few days, than if I had not taken one at all.

[Jack-of-all-trades]

This is similar to what my pain doc said was happening with me. Of course, at first, I thought he was full of crap. I had pain, I felt pain and thought he just thought I was a druggie. Once I decided that I had had enough of the drugs and pain and was ready for a change, then I decided to test his 'theory'. Basically, he said that I was feeling pain, but it was being intensified by the drugs. I would however, get relief from opiods. But, I have found that my overall pain is way less without the opiods. I have also noticed, that when I do take a Vicodin for pain, I hurt more for the next few days, than if I had not taken one at all.

Just a thought, hydrocodone has a short half life, definitely not into days. You might be more active after taking your Vicodin, aggravating your pain source.

[scduggan]

Hey,
I need to jump in with a couple of questions about this subject. What about this hypersensitivity or tolerance for someone who is not even two weeks post surgery? I had a Freedom disc implanted on 2/18 and my surgeon gave me Norco with strict instuctions to never take more than six per day. I am struggling and, in my opinion, not as far along as I should be because I have been on hydrocodone for months. I will get to the the end of the day and realize I only walked once or twice. I am pretty much useless that last hour of the four hour med cycle. Prior to surgery I only took two or sometimes three 10mg. pills per day. Six sounds like a lot but when you factor in taking one in the middle of the night....it is a little sparse. I am sure I have a tolerance. It DOES help but seems to only be taking off the edge then crashing and burning in about 2 1/2 to 3 hours. Tomorrow I see my local surgeon for a two week check-up. I am a MOUSE about asking for something else. I don't feel like I need something necessarily stronger....just something my body will recognize as different. Could I be hypersensitive this close to surgery? I know I have a tolerance for the hydrocodone. It is scary to feel like I need to venture out in to deeper waters, but I feel like it is what I need for the short term. Is there a "standard goal" for spine patients about when it is ideal to put the narcotics completely aside? I was hoping to be over and done with them in six weeks. I have a sister-in-law who is the classic drug addict. I think seeing her and the negative impact she has on so many makes me very fearful of that slippery slope. Justin and Jack, I am hoping you will give your opinions...for you are wise grasshoppas!
CD

[Justin]

Hey,
I need to jump in with a couple of questions about this subject. What about this hypersensitivity or tolerance for someone who is not even two weeks post surgery?

Hypersensitivity should not be an issue for you at this time post-op. You have experienced voluntary-induced trauma on your body and your body is responding naturally by increasing your pain levels. You are only two weeks post-op, which is still very early in the recovery process.

I had a Freedom disc implanted on 2/18 and my surgeon gave me Norco with strict instuctions to never take more than six per day. I am struggling and, in my opinion, not as far along as I should be because I have been on hydrocodone for months. I will get to the the end of the day and realize I only walked once or twice. I am pretty much useless that last hour of the four hour med cycle. Prior to surgery I only took two or sometimes three 10mg. pills per day. Six sounds like a lot but when you factor in taking one in the middle of the night....it is a little sparse. I am sure I have a tolerance. It DOES help but seems to only be taking off the edge then crashing and burning in about 2 1/2 to 3 hours.

Tolerance is inevitable with narcotics--everyone faces it at some point--it's just normal physiology and not something you did to influence this or "cause" you to become tolerant. Inevitably, Spine Patients on narcotics will have to increase their dosage due to tolerance, especially if you have been on narcotic therapy long-term.

You can always cut your medication in half to help avoid the peaks and valleys between doses.

Tomorrow I see my local surgeon for a two week check-up. I am a MOUSE about asking for something else. I don't feel like I need something necessarily stronger....just something my body will recognize as different. Could I be hypersensitive this close to surgery? I know I have a tolerance for the hydrocodone. It is scary to feel like I need to venture out in to deeper waters, but I feel like it is what I need for the short term. Is there a "standard goal" for spine patients about when it is ideal to put the narcotics completely aside? I was hoping to be over and done with them in six weeks. I have a sister-in-law who is the classic drug addict. I think seeing her and the negative impact she has on so many makes me very fearful of that slippery slope. Justin and Jack, I am hoping you will give your opinions...for you are wise grasshoppas!
CD

I would venture to say that you are not hypersensitive. There is no standard for Spine Patients in which to be free from narcotics. Our situations (past medical history), response to pain, the rate at which we heal, etc. will all inherently vary from one patient to the next. As such, treatment to pain post-op varies greatly.

Ask your surgeon about switching your medications to a long-acting opioid and a break-through pain med in the short-term. You will have much better coverage of pain with the long-acting medication and should subsequently only need the break-through med when you are really hurting.

Of course, I'm not a doctor, so please follow-up with your surgeon and take my recommendations with a grain of salt.

Good luck and keep us posted.

[KBear]

Only 2 weeks out from surgery, I would be begging for more drugs... Prior to surgery, I was on Kadian (long acting morphine) 20mcg 2xday & 5-6 10mg Vicodin a day. I got off the Kadian a few weeks prior to surgery. After surgery, mind you, I am very tolerant to pain meds (I have always been.... even before I had back problems), I was on 14 10mg Oxycodone a day! I was able to get down to 6 a day and then switched back to the Vicodin, at 6 a day (this was a few months down the road). At like the 6 month post op mark, I was still not being able to function and walk and do what I knew I should be doing to heal; because I just hurt so bad. I had the exact same problem with the relief for about an hour, then I would be back hurting. That is when my doctor put me back on Kadian twice a day. It made a big difference. I think it allowed my body to be out of pain and heal.... otherwise I was in so much pain, I was just tense and non-moving. I seriously would not worry about meds at this point, you just had MAJOR surgery.