Hyperalgesia in Methadone Patients: Can it be Treated?
(2009)
Abstract :
DESCRIPTION (provided by applicant): Addressing the under-treatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01 -115). In fact, the under-treatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid analgesics, makes them a population uniquely vulnerable to the under treatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced. In the proposed series of studies, the Principal Investigator (a first-time RO1 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)-antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia.
| Project Number : | 5R01DA015463-05 |
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| ICD : | NATIONAL INSTITUTE ON DRUG ABUSE |
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| IRG : | ZDA1 |
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| Project Terms : | analgesic, drug adverse effect, hyperalgesia, methadone anticonvulsant, codeine, dextromethorphan, drug abuse chemotherapy, drug screening /evaluation, human therapy evaluation, pain threshold clinical research, human subject, patient oriented research |
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The Effects of Pain on Leukocyte CAM Expression
(2008)
Abstract :
Pain is a phenomenon of seminal interest to nursing; providing pain relief and easing suffering have been central activities within the domain of nursing practice since the profession's inception. Nurses understand that unrelieved pain brings with it a range of detrimental health effects, yet still to be explored is how pain, as an adrenergic and nociceptive stressor, might impact on inflammatory processes via its direct and indirect effects on cellular adhesion molecule (CAM) levels. Known responses of both the sympathetic nervous system to stress and the sensory nervous system to nociceptive stimuli suggest that pain could be an especially potent inducer of CAM expression. The proposed and revised application represents an expansion of the principal investigator's expertise in pain physiology to include the effects of pain on immune and inflammatory parameters via multidisciplinary collaboration with nationally-recognized immunologists, and completion of a pilot study exploring the effects of experimental pain on CAM levels in healthy controls. The roles of affective stress, epinephrine, norepinephrine, and interleukin-6 in pain-induced CAM expression will be described in a small sample using an experimental design with repeated measures and randomly ordered experimental (low-stress pain, high-stress pain) and control (no pain) conditions. Conceptualizing pain as a potent and unique stressor, its effects on concomitant inflammatory processes is clearly an area worthy of nursing investigation, with important health implications for many patients, particularly those suffering from chronic inflammatory diseases such as atherosclerosis, inflammatory bowel disease, and rheumatoid arthritis.
| Project Number : | 5R03NR009106-02 |
|---|
| ICD : | NATIONAL INSTITUTE OF NURSING RESEARCH |
|---|
| IRG : | NSCF |
|---|
| Project Terms : | cell adhesion molecule, gene expression, immune response, inflammation, pain, psychoneuroimmunology acute phase protein, electrostimulus, epinephrine, interleukin 6, norepinephrine, nursing research clinical research, enzyme linked immunosorbent assay, human subject |
|---|
Hyperalgesia in Methadone Patients: Can it be Treated?
(2008)
Abstract :
DESCRIPTION (provided by applicant): Addressing the under-treatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01 -115). In fact, the under-treatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid analgesics, makes them a population uniquely vulnerable to the under treatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced. In the proposed series of studies, the Principal Investigator (a first-time RO1 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)-antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia.
| Project Number : | 5R01DA015463-03 |
|---|
| ICD : | NATIONAL INSTITUTE ON DRUG ABUSE |
|---|
| IRG : | ZDA1 |
|---|
| Project Terms : | analgesic, drug adverse effect, hyperalgesia, methadone anticonvulsant, codeine, dextromethorphan, drug abuse chemotherapy, drug screening /evaluation, human therapy evaluation, pain threshold clinical research, human subject, patient oriented research |
|---|
Hyperalgesia in Methadone Patients: Can it be Treated?
(2008)
Abstract :
DESCRIPTION (provided by applicant): Addressing the under-treatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01 -115). In fact, the under-treatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid analgesics, makes them a population uniquely vulnerable to the under treatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced. In the proposed series of studies, the Principal Investigator (a first-time RO1 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)-antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia.
| Project Number : | 5R01DA015463-04 |
|---|
| ICD : | NATIONAL INSTITUTE ON DRUG ABUSE |
|---|
| IRG : | ZDA1 |
|---|
| Project Terms : | analgesic, drug adverse effect, hyperalgesia, methadone anticonvulsant, codeine, dextromethorphan, drug abuse chemotherapy, drug screening /evaluation, human therapy evaluation, pain threshold clinical research, human subject, patient oriented research |
|---|
The Effects of Pain on Leukocyte CAM Expression
(2007)
Abstract :
Pain is a phenomenon of seminal interest to nursing; providing pain relief and easing suffering have been central activities within the domain of nursing practice since the profession's inception. Nurses understand that unrelieved pain brings with it a range of detrimental health effects, yet still to be explored is how pain, as an adrenergic and nociceptive stressor, might impact on inflammatory processes via its direct and indirect effects on cellular adhesion molecule (CAM) levels. Known responses of both the sympathetic nervous system to stress and the sensory nervous system to nociceptive stimuli suggest that pain could be an especially potent inducer of CAM expression. The proposed and revised application represents an expansion of the principal investigator's expertise in pain physiology to include the effects of pain on immune and inflammatory parameters via multidisciplinary collaboration with nationally-recognized immunologists, and completion of a pilot study exploring the effects of experimental pain on CAM levels in healthy controls. The roles of affective stress, epinephrine, norepinephrine, and interleukin-6 in pain-induced CAM expression will be described in a small sample using an experimental design with repeated measures and randomly ordered experimental (low-stress pain, high-stress pain) and control (no pain) conditions. Conceptualizing pain as a potent and unique stressor, its effects on concomitant inflammatory processes is clearly an area worthy of nursing investigation, with important health implications for many patients, particularly those suffering from chronic inflammatory diseases such as atherosclerosis, inflammatory bowel disease, and rheumatoid arthritis.
| Project Number : | 1R03NR009106-01A1 |
|---|
| ICD : | NATIONAL INSTITUTE OF NURSING RESEARCH |
|---|
| IRG : | NSCF |
|---|
| Project Terms : | cell adhesion molecule, gene expression, immune response, inflammation, pain, psychoneuroimmunology acute phase protein, electrostimulus, epinephrine, interleukin 6, norepinephrine, nursing research clinical research, enzyme linked immunosorbent assay, human subject |
|---|
Hyperalgesia in Methadone Patients: Can it be Treated?
(2007)
Abstract :
DESCRIPTION (provided by applicant): Addressing the under-treatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01 -115). In fact, the under-treatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid analgesics, makes them a population uniquely vulnerable to the under treatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced. In the proposed series of studies, the Principal Investigator (a first-time RO1 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)-antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia.
| Project Number : | 1R01DA015463-01 |
|---|
| ICD : | NATIONAL INSTITUTE ON DRUG ABUSE |
|---|
| IRG : | ZDA1 |
|---|
| Project Terms : | analgesic, drug adverse effect, hyperalgesia, methadone anticonvulsant, codeine, dextromethorphan, drug abuse chemotherapy, drug screening /evaluation, human therapy evaluation, pain threshold clinical research, human subject, patient oriented research |
|---|
Hyperalgesia in Methadone Patients: Can it be Treated?
(2007)
Abstract :
DESCRIPTION (provided by applicant): Addressing the under-treatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01 -115). In fact, the under-treatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid analgesics, makes them a population uniquely vulnerable to the under treatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced. In the proposed series of studies, the Principal Investigator (a first-time RO1 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)-antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia.
| Project Number : | 5R01DA015463-02 |
|---|
| ICD : | NATIONAL INSTITUTE ON DRUG ABUSE |
|---|
| IRG : | ZDA1 |
|---|
| Project Terms : | analgesic, drug adverse effect, hyperalgesia, methadone anticonvulsant, codeine, dextromethorphan, drug abuse chemotherapy, drug screening /evaluation, human therapy evaluation, pain threshold clinical research, human subject, patient oriented research |
|---|
PAIN TOLERANCE AND ANALGESIC RESPONSE IN OPIATE ADDICTS
(1999)
Abstract :
NIDA's recently released (6/94) Program Announcement (#94-070) on Prescription Drug Use, Abuse and Diversion reflects a growing appreciation among clinicians and researchers in both the areas of pain and addiction of the complexities involved in prescribing opioid analgesics, which have clear therapeutic indications, to patients with a known history of drug abuse. The proposed RO3 application, with a relatively new researcher serving as principal investigator, describes a necessary first step to estimating the risk of analgesic abuse by opiate addicts in pain, and developing appropriate practice and regulatory guidelines for analgesic prescription to known drug abusers. Pain tolerance and analgesic response will be described in two samples of opiate-maintained drug abusers (54 methadone-maintained and 54 buprenorphine-maintained male and female subjects) in comparison to a sample (n=54) of non-dependent controls matched on race and gender. Pain tolerance is operationalized as tolerance to a standard cold-pressor trial. Analgesic response is operationalized as change in cold-pressor trial tolerance following double-blind challenges to an opioid analgesic (Dilaudid, 3 mg., PO), a nonsteroidal anti-inflammatory analgesic (Toradol, 10 mg., PO), and placebo, using a Latin Square design. The differential effects of opiate maintenance agent and analgesic agent on pain tolerance will be the primary subjects of analyses. It is anticipated that the findings from the proposed study will provide preliminary information on analgesic need and response in opiate- maintained drug abusers, and lead to the subsequent development of larger evaluations of appropriate analgesic prescription to individuals with a history of drug abuse. Studies of pain tolerance and analgesic response in samples of opiate addicts and other drug abusers, not in treatment, and experiencing acute or chronic pain in clinical settings, are logical extensions of the proposed work to increase the generalizability and utility of the findings in practice and regulatory contexts.
| Project Number : | 5R03DA009866-02 |
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| ICD : | NATIONAL INSTITUTE ON DRUG ABUSE |
|---|
| IRG : | SRCD |
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| Project Terms : | analgesia, analgesic, drug addiction, human therapy evaluation, opiate alkaloid, pain threshold buprenorphine, drug abuse chemotherapy, methadone human subject |
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PAIN TOLERANCE AND ANALGESIC RESPONSE IN OPIATE ADDICTS
(1997)
Abstract :
NIDA's recently released (6/94) Program Announcement (#94-070) on Prescription Drug Use, Abuse and Diversion reflects a growing appreciation among clinicians and researchers in both the areas of pain and addiction of the complexities involved in prescribing opioid analgesics, which have clear therapeutic indications, to patients with a known history of drug abuse. The proposed RO3 application, with a relatively new researcher serving as principal investigator, describes a necessary first step to estimating the risk of analgesic abuse by opiate addicts in pain, and developing appropriate practice and regulatory guidelines for analgesic prescription to known drug abusers. Pain tolerance and analgesic response will be described in two samples of opiate-maintained drug abusers (54 methadone-maintained and 54 buprenorphine-maintained male and female subjects) in comparison to a sample (n=54) of non-dependent controls matched on race and gender. Pain tolerance is operationalized as tolerance to a standard cold-pressor trial. Analgesic response is operationalized as change in cold-pressor trial tolerance following double-blind challenges to an opioid analgesic (Dilaudid, 3 mg., PO), a nonsteroidal anti-inflammatory analgesic (Toradol, 10 mg., PO), and placebo, using a Latin Square design. The differential effects of opiate maintenance agent and analgesic agent on pain tolerance will be the primary subjects of analyses. It is anticipated that the findings from the proposed study will provide preliminary information on analgesic need and response in opiate- maintained drug abusers, and lead to the subsequent development of larger evaluations of appropriate analgesic prescription to individuals with a history of drug abuse. Studies of pain tolerance and analgesic response in samples of opiate addicts and other drug abusers, not in treatment, and experiencing acute or chronic pain in clinical settings, are logical extensions of the proposed work to increase the generalizability and utility of the findings in practice and regulatory contexts.
| Project Number : | 1R03DA009866-01 |
|---|
| ICD : | NATIONAL INSTITUTE ON DRUG ABUSE |
|---|
| IRG : | SRCD |
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PERCEPTION DRUG PREFERENCE AND PAIN IN DRUG USERS
(1992)
Abstract :
Addressing complaints of pain in the hospitalized substance-abusing patient poses a significant and challenging nursing care problem. Nurses practicing in acute care settings are well-aware of the difficulties in objectively assessing the substance abuser's pain. Patient manipulation regarding medication regimens is well-documented. Related to their diminished ability to self-care and promote their own health, these persons are extremely likely to become ill and require medical care, which typically result in the response of pain. The objective of the proposed research is to develop a better understanding of the experience of pain for the substance abuser so that nurses can better assess and manage these patients' discomfort. The specific aim of the study is to learn if their pain experience is related to their perceptual style, which is also expected to be manifest in their preferred drug of use. Based upon Petrie's (1967) theory of perceptual reactance, persons who characteristically augment or magnify sensory stimuli would be relatively pain intolerant and prefer drugs which restrict subjective sensory experience, whereas persons who perceptually reduce or attenuate the same would be more pain tolerant and prefer the subjective effects of sensory- expanding drugs. Utilizing a descriptive, survey research design, the relationships among perceptual reactance, drug of choice and pain perception in known substance abusers will be explored. Perceptual reactance in a convenience sample of 60 substance abusers currently in treatment and 60 recovering substance abusers will be described using Vando's (1969) psychometric scale and basal skin conductance levels. Drug of choice will be dichotomized as either a sensory-expanding or sensory-restricting drug and be operationalized by responses to The Addiction Severity Index and a single multiple-choice question assessing drug preference. Pain perception will be measured as tolerance to a single cold pressor trial. Correlations among these variables will be calculated, as will a multiple regression equation to learn of the predictive value of perceptual style, drug of choice and other demographic variables gleaned from the Addiction Severity Index in predicting pain tolerance. Identifying the variables which influence substance abusers' pain experience will enable health care professionals to more effectively comfort these patients and explore non-pharmacological interventions which address perceptual preferences and tolerances.
| Project Number : | 1R03HS006964-01 |
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| ICD : | AGENCY FOR HEALTHCARE RESEARCH AND QUALITY |
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| IRG : | SRC |
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| Project Terms : | drug abuse, pain tolerance, perception, preference, sensory threshold nursing intervention electrode, female, human clinical subject, human volunteer subject, male, questionnaire, statistics /biometry, urinalysis |
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