Patients in this group have shown an increased sensitivity to cold pressor pain when compared with former patients who were no longer using methadone or healthy controls. In addition, there have been a significant number of studies that have demonstrated the development of OIH in patients exposed to opioids for short duration.
This occurrence has been documented in the perioperative period and also in studies recruiting healthy volunteers who have been acutely exposed to opioids in experimental settings. OIH can clinically manifest as hyperalgesia increased response to painful stimuli , allodynia painful response to normally innocuous stimulus , or both. Pain is typically described in an anatomically distinct region and is of a different quality than the original pain presentation.
The important dilemma facing the clinician in making a diagnosis is to distinguish OIH from other phenomena such as opioid tolerance, disease progression, opioid withdrawal, opioid addiction, or pseudo addiction. Differential diagnosis for OIH 6 , 7. These receptors are distributed widely in the brain, spinal cord, peripheral afferent nerve terminals, and other organs.
The rostral ventral medulla RVM and periaqueductal grey areas of the brainstem also express particularly high levels of opioid receptors. Opioid receptors are coupled with inhibitory G-proteins and their activation leads to closing of voltage-sensitive calcium channels and stimulation of potassium efflux.
These changes lead to hyperpolarization, thereby reducing neuronal excitability and nociceptive afferent transmission. Investigations have revealed that in addition to these inhibitory effects, opioid receptors can also have excitatory effects on cells. In vitro studies have shown that excitatory actions of morphine can be observed at doses fold smaller than clinical doses.
This has supported a theory of bi-modally acting opioids. In clinical settings, this excitatory function is masked as the high doses in clinical use activate inhibitory functions.
This mechanism of stimulation has been postulated to involve G-protein-linked secondary messenger signalling pathways, which are excitatory in function. A number of different opioid molecules exist morphine, fentanyl, buprenorphine, etc. This explains the phenomenon of incomplete cross-tolerance, which may be used to overcome opioid tolerance by using opioid rotation strategies.
The exact mechanism of OIH is not clearly understood. However, several theories exist which are briefly summarized below. Glutamate is thought to play a central role in the development of OIH. Mao and colleagues 9 have shown that prolonged morphine administration induces down-regulation of spinal glutamate transporters in the spinal cord, leading to increased glutamate levels available for NMDA receptors. Glutamate-associated activation of NMDA receptors can cause spinal neurone sensitization, possibly contributing to the development of OIH. This phenomenon has been prevented by NMDA receptor inhibition.
These increased levels of dynorphins lead to the release of excitatory neuropeptides such as calcitonin gene-related peptide CGRP from primary afferent neurones and cholecystokinin CCK from neurones. These excitatory neuropeptides act as pronociceptive agents that enhance nociceptive inputs at the spinal level. Subsets of neurones within the RVM can mediate nociceptive transmission.
These cells are identified as on cells ON , which facilitate incoming pain signals and off cells OFF which inhibit pain signals. Chronic exposure to opioids may alter G-protein activity, such that the G-protein second messenger systems are converted from an inhibitory to an excitatory-coupled mode via alteration in a specific glycolipid complex on the neuronal cell membrane.
This increase in excitatory activity has emerged to be a possible contributor to analgesic tolerance and OIH. In vitro studies have demonstrated that when opioids are combined with ultra low doses of an opioid antagonist, excitatory effects can be blocked. Activation of serotonergic 5HT 3 and 5HT 2 receptors in certain chronic pain states may be involved in the development of OIH by shifting the balance from descending inhibitory control towards pro-nociception.
Activation of Substance P, alteration of cytokine production, and changes in calcium channels and nitric oxide synthetase have all been implicated in the development of OIH in various studies.
QST involves application of different mechanical and thermal stimuli of controlled intensity to measure an individual's pain threshold. It has been utilized in the diagnosis of painful conditions such as peripheral neuropathies and radiculopathies. In patients managed with long-term opioid therapy, QST has demonstrated changes in their perception of pain. For example, individuals with histories of opioid abuse being treated with methadone have shown reduced pain tolerance and enhanced sensitivity to cold pressor stimuli when compared with QST responses in control subjects.
In the laboratory setting, QST has been used to assist in the identification of remifentanil-induced hyperalgesia. For example, Compton and Athanasos 12 could document changes in QST scores between an individual's baseline pain sensitivity and the pain sensitivity at repeated intervals after a dose of remifentanil.
Weber, Lena; Yeomans, David C. Correspondence: David C. To comment please Log-in. All rights Reserved. Clinical evidence of OIH has primarily come from observational studies of patients exposed to long-term methadone maintenance therapy for the treatment of substance dependence. Management of opioid induced hyperalgesia requires opioid dose reduction or changing to an alternative opioid preparation.
However, the nature of test results can vary depending on the modality of testing used e. Further work will be needed to refine these tools before they can be used for widespread clinical use.
BACKGROUND: Opioid-induced hyperalgesia (OIH) refers to a phenomenon whereby opioid administration results in a lowering of pain threshold, clinically. Pain Med. Oct;16 Suppl 1:S doi: /pme Opioid Induced Hyperalgesia. Yi P(1), Pryzbylkowski P(1). Author information.
Reducing the total dose of opioid being consumed can mitigate OIH. This can be accomplished by improving analgesia through the use of co-analgesics and interventional strategies as discussed below. This can include the combination of anticonvulsants, antidepressants, and non-steroidal anti-inflammatory drugs NSAIDs , as appropriate, for treating patients with neuropathic pain or nociceptive pain. These opioid-sparing therapies form the basis for the prevention of opioid-related adverse effects.
Interventional therapies can block nociceptive input and often serve a dual function of assisting in diagnosing pain generators and providing therapeutic benefit. Regional blocks, peripheral nerve blocks, and spinal cord stimulation can be considered as alternative management strategies for chronic painful conditions in lieu of or in conjunction with oral analgesics. Studies have shown that cognitive behavioural therapy can be an effective treatment strategy in patients with chronic pain conditions. With psychological interventions, pain and disability may improve, leading to opportunities to reduce opioid dosages.
An important aspect in the management of OIH is to establish the diagnosis. An initial step to consider is to increase the dose of opioids and evaluate for increased efficacy. If pain is reduced with the increased dose, this suggests the presence of opioid tolerance rather than OIH. Alternatively, if the pain worsens, this may suggest that the patient is experiencing OIH. The following pharmacological strategies can help to manage OIH. The majority of respondents identified as palliative care specialists.
The three features felt to be most suggestive of OIH were; escalating pain despite increasing opioids, demonstrable hyperalgesia or allodynia and a more diffuse pain distribution away from pre-existing pain sites. Most clinicians utilized more than one approach when OIH was encountered.
The commonest of these were opioid reduction, opioid rotation and optimization of adjuvant analgesia. Conclusions: Our survey found a higher rate of reported observation of OIH amongst clinicians than might have been anticipated given debate about the existence of OIH in humans outside of a research environment. These results suggest that many palliative care clinicians perceive OIH to be a genuine issue for their patients.
Article Tools. Is opioid-induced hyperalgesia a genuine issue for palliative care patients and clinicans?
vipauto93.ru/profiles/software/come-faccio-a-sapere-se-liphone-ancora-in-garanzia.php Opioid-induced hyperalgesia can also be seen when those drugs are administered for a short period 3. Opioid-induced hyperalgesia affects animals and humans who receive opioids and drug-addicts on methadone maintenance 1,2, In opioid-dependent individuals, a heightened sensitivity to pain is observed, and its interruption causes hyperalgesia.
Sensitivity in areas of trauma is observed 1 , but the type and location of this pain can be different from the original pain 2,3,7,8. Opioid-induced hyperalgesia can develop differently for different types of pain 1. In animals, hyperalgia, which varies according to the different stimuli mechanical, thermal is also observed after discontinuation of the opioid 1. Opioid-dependent patients show sensitivity to cold, but not to electrical and mechanical stimuli 1. Increased sensitivity to cold and heat without affecting pressure sensitivity can be observed 1.
A difference in chronic oncologic pain and nononcologic pain was not observed 4. After acute administration of opioid the anti-nociceptive effect is seen during 1 to 5 hours followed by a reduction of pain threshold for several hours up to 10 days 2,4,8, The use of long-acting opioids after surgeries can mask hyperalgesia 4.
With chronic use, an anti-nociceptive effect is seen on the first day followed by the loss of the effect or even progressive hyperalgia 1. Evaluation of hyperalgesia can be done through the threshold for mechanical stimulus per-incisional, in the palmar region of the carpus, or in the interior face of the forearm or with the coldtolerance test 8,9.
Animals recovering from OIH remain sensitized to the effects of hyperalgesia of opioids with greater vulnerability to pain 1. This phenomenon is reversible to some extent, but it requires a long period of abstinence 3. Therefore, any chronic or acute use of opioids can cause hyperalgesia. Hyperalgesia is associated with central sensitization with reduction in pain threshold, expansion of the receptive field stimulation of a neuron in the posterior horn of the spinal cord activates a greater peripheral area , and increase in the answer to the nociceptive stimulus.
The pain is more severe than the original or initial pain, is not well defined in terms of quality and location, and it is associated with a reduction in the threshold and tolerability 5. The phenomenon in which exposure to opioids leads to a reduction on its effect, requiring larger doses to maintain it, is called tolerance, i.
It reflects the reduction in the sensitivity to opioids, which is due to desensitization of the anti-nociceptive pathway 3. In desensitization of the anti-nociceptive pathway, G-protein receptors are incapable of reducing intracellular cyclic AMP and, consequently, the inward movement of sodium and calcium.
A reduction in membrane receptors by internalization is another reason for tolerance 3. It is characterized by a reduction of the analgesic potency and it improves with an increase in the dose of the medication or changing of the opioid 1. Pharmacologically, they are distinct phenomena 2. They can involve opposite cellular mechanisms, with desensitization tolerance and sensitization OIH 6. In clinical practice it is difficult, and even impossible to distinguish the two phenomena. Hyperalgesia can mask anti-nociception producing the impression of tolerance 7.
Both conditions probably coexist and evidence that tolerance and hyperalgesia share several cellular mechanisms and some neurotransmitters and receptors systems, including dynorphin, protein kinase-C, NMDA receptors, nitric oxide synthase, heme oxigenase, and others exists 1. Other cellular mechanisms differ in tolerance and hyperalgesia 3. However, the mechanisms might not contribute in the same proportion for the loss of the analgesic effect.