Are ACOs Ready to be Accountable for Medication Use?

BACKGROUND: Accountable care organizations (ACOs) have the potential to lower costs and improve quality through incentives and coordinated care. However, the design brings with it many new challenges. One such challenge is the optimal use of pharmaceuticals. Most ACOs have not yet focused on this integral facet of care, even though medications are a critical component to achieving the lower costs and improved quality that are anticipated with this new model. OBJECTIVE: To evaluate whether ACOs are prepared to maximize the value of medications for achieving quality benchmarks and cost offsets. METHODS: During the fall of 2012, an electronic readiness self-assessment was developed using a portion of the questions and question methodology from the National Survey of Accountable Care Organizations, along with original questions developed by the authors. The assessment was tested and subsequently revised based on feedback from pilot testing with 5 ACO representatives. The revised assessment was distributed via e-mail to a convenience sample (n=175) of ACO members of the American Medical Group Association, Brookings-Dartmouth ACO Learning Network, and Premier Healthcare Alliance. RESULTS: The self-assessment was completed by 46 ACO representatives (26% response rate). ACOs reported high readiness to manage medications in a few areas, such as transmitting prescriptions electronically (70%), being able to integrate medical and pharmacy data into a single database (54%), and having a formulary in place that encourages generic use when appropriate (50%). However, many areas have substantial room for improvement with few ACOs reporting high readiness. Some notable areas include being able to quantify the cost offsets and hence demonstrate the value of appropriate medication use (7%), notifying a physician when a prescription has been filled (9%), having protocols in place to avoid medication duplication and polypharmacy (17%), and having quality metrics in place for a broad diversity of conditions (22%). CONCLUSIONS: Developing the capabilities to support, monitor, and ensure appropriate medication use will be critical to achieve optimal patient outcomes and ACO success. The ACOs surveyed have embarked upon an important journey towards this goal, but critical gaps remain before they can become fully accountable. While many of these organizations have begun adopting health information technologies that allow them to maximize the value of medications for achieving quality outcomes and cost offsets, a significant lag was identified in their inability to use these technologies to their full capacities. In order to provide further guidance, the authors have begun documenting case studies for public release that would provide ACOs with examples of how certain medication issues have been addressed by ACOs or relevant organizations. The authors hope that these case studies will help ACOs optimize the value of pharmaceuticals and achieve the "triple aim" of improving care, health, and cost. DISCLOSURES: There was no outside funding for this study, and the authors report no conflicts of interest related to the article. Concept and design were primarily from Dubois and Kotzbauer, with help from Feldman, Penso, and Westrich. Data collection was done by Feldman, Penso, Pope, and Westrich, and all authors participated in data interpretation. The manuscript was written primarily by Westrich, with help from all other authors, and revision was done primarily by Lustig and Westrich, with help from all other authors.

The Central Role of Physician Leadership for Driving Change in Value-Based Care Environments.

BACKGROUND: In 2013, it was reported that about 1 of every 3 U.S. adults has hypertension. Of these 70 million individuals, approximately 50% have their blood pressure under control. Achieving hypertension control, especially in at-risk populations, requires a multipronged approach that includes lifestyle modifications and pharmacological treatment. As provider groups, hospital systems, and integrated delivery networks optimize their care processes to promote population health activities in support of the accountable care organization (ACO) model of care, managing hypertension and other chronic diseases will be essential to their success. A critical aspect of managing populations in an ACO environment is optimization of care processes among providers to increase care efficiency and improve patient outcomes. PROGRAM DESCRIPTION: Launched in 2013, Measure Up/Pressure Down is a 3-year campaign developed by the American Medical Group Foundation (AMGF) to reduce the burden of high blood pressure. The goal of the campaign is for participating medical groups, health systems, and other organized systems of care to achieve hypertension control for 80% of their patients with high blood pressure by 2016, according to national standards. The role of physician leadership at Cornerstone Health Care (CHC) and Summit Medical Group (SMG) in facilitating organizational change to improve hypertension management through the implementation of the Measure Up/Pressure Down national hypertension campaign is examined. OBSERVATIONS: Using patient stratification via its electronic health record, SMG identified 16,000 patients with hypertension. The baseline percentage of hypertension control for this patient population was 66%. Within 7 months, SMG was able to meet the 80% goal set forth by the AMGF's Measure Up/Pressure Down campaign. CHC diagnosed 25,312 patients with hypertension. The baseline percentage of hypertension control for this subgroup of patients was 51.5% when the initiative was first implemented. To date, the organization has achieved 72% hypertension control for at-risk patients and continues work towards the 80% campaign goal. The implementation of the Measure Up/Pressure Down campaign by CHC and SMG provides some valuable lessons. To further explore important aspects of successfully implementing the Measure Up/Pressure Down campaign in real-world settings, 6 key themes were identified that drove quality improvement and may be helpful to other organizations that implement similar quality improvement initiatives: (1) transitioning to value-based payments, (2) creating an environment for success, (3) leveraging program champions, (4) sharing quality data, (5) promoting care team collaboration, and (6) leveraging health information technology. IMPLICATIONS: The strategies employed by SMG and CHC, such as leveraging data analysis to identify at-risk patients and comparing physician performance, as well as identifying leaders to institute change, can be replicated by an ACO or a managed care organization (MCO). An MCO can provide data analysis services, sparing the provider groups the analytic burden and helping the MCO build a more meaningful relationship with their providers. DISCLOSURES: No outside funding supported this project. The authors declare no conflicts of interest. The authors are members of the Working Group on Optimizing Medication Therapy in Value-Based Healthcare. Odgen is employed by Cornerstone Health Care; Brenner is employed by Summit Medical Group; and Penso is employed by American Medical Group Association. Lustig, Westrich, and Dubois are employed by the National Pharmaceutical Council, an industry-funded health policy research organization that is not involved in lobbying or advocacy. Study concept and design were contributed by Lustig, Penso, Westrich, and Dubois. Lustig, Ogden, Brenner, and Penso collected the data, and data interpretation was performed by all authors. The manuscript was written primarily by Lustig, along with the other authors, and revised by Lustig, Penso, Westrich, and Dubois, assisted by Ogden and Brenner.

Using an Electronic Medication Refill System to Improve Provider Productivity in an Accountable Care Setting.

BACKGROUND: Even within fully integrated health care systems, primary care providers (PCPs) often lack support for medication management. Because challenges with conducting medication reconciliation, improving adherence, and achieving optimal patient outcomes continue to be prevalent nationally, it is critical that PCPs are provided the resources and support they need to provide high-quality, patient-centered care in an accountable care environment. PROGRAM DESCRIPTION: Sharp Rees-Stealy Medical Group uses a fully electronic medication refill system that allows for a centralized team to manage all incoming requests. Over time, 16 disease-specific protocols were created that allowed the pharmacy team to absorb approximately 80% of incoming refill requests for all enrolled PCPs. The refill clinic assessed all clinic information that a PCP would normally review in order to approve a refill. Tasks performed by the clinical pharmacists included medication reconciliation, dosage adjustment, and coordination of distribution from external mail order and retail pharmacies. OBSERVATIONS: In 2014, the number of tasks related to refill management reviewed by the refill/medication therapy management service totaled 302,592, resulting in 140,350 refill authorizations and multiple interventions related to medication use. Physicians have estimated that the service provides between 20 and 30 minutes of time savings per day. Assuming an annual PCP salary of around $200,000, 20 to 30 minutes per day would amount to $33 to $50 saved per day per physician. The savings is even higher when time savings from other clinical staff is included. IMPLICATIONS: The development of this electronic medication refill service has provided the following important lessons: (a) organizations rely on a leader or champion to push through process reforms--this program started with reluctant physicians first to determine best practices; (b) the lack of clinical pharmacist profiles within electronic health records (EHR) is a serious concern, since the creation of these profiles may not be easy or timely; and (c) PCPs working within an EHR environment will quickly embrace the idea of a service that can save them up to 30 minutes per day. With PCPs continuing to take on additional population health management tasks in accountable care organizations, pharmacists can provide workload offsets by meaningfully contributing to medication-related care.

Best practices: an electronic drug alert program to improve safety in an accountable care environment.

BACKGROUND: The accountable care organization (ACO), one of the most promising and talked about new models of care, focuses on improving communication and care transitions by tying potential shared savings to specific clinical and financial benchmarks. An important factor in meeting these benchmarks is an ACO's ability to manage medications in an environment where medical and pharmacy care has been integrated. The program described in this article highlights the critical components of Marshfield Clinic's Drug Safety Alert Program (DSAP), which focuses on prioritizing and communicating safety issues related to medications with the goal of reducing potential adverse drug events. PROGRAM DESCRIPTION: Once the medication safety concern is identified, it is reviewed to evaluate whether an alert warrants sending prescribers a communication that identifies individual patients or a general communication to all physicians describing the safety concern. Instead of basing its decisions regarding clinician notification about drug alerts on subjective criteria, the Marshfield Clinic's DSAP uses an internally developed scoring system. The scoring system includes criteria developed from previous drug alerts, such as level of evidence, size of population affected, severity of adverse event identified or targeted, litigation risk, available alternatives, and potential for duration of medication use. Each of the 6 criteria is assigned a weight and is scored based upon the content and severity of the alert received.  OBSERVATIONS: In its first 12 months, the program targeted 6 medication safety concerns involving the following medications: topiramate, glyburide, simvastatin, citalopram, pioglitazone, and lovastatin. Baseline and follow-up prescribing data were gathered on the targeted medications. Follow-up review of prescribing data demonstrated that the DSAP provided quality up-to-date safety information that led to changes in drug therapy and to decreases in potential adverse drug events. In aggregate, nearly 10,000 total potential adverse drug events were identified with baseline data from the DSAP initiatives, and nearly 8,000 were resolved by changes in prescribing.  IMPLICATIONS: Implications and additional thoughts from The Working Group on Optimizing Medication Therapy in Value-Based Healthcare were provided for the following categories: leveraging electronic health records, importance of data collection and reassessment, preventing alert fatigue utilizing various techniques, relevance to ACO quality measurement, and limitations of a retrospective system. RECOMMENDATIONS: While health information technologies have been recognized as a cornerstone for an ACO's success, additional research is needed on comparing these types of technological innovations. Future research should focus on reviewing comparable scoring criteria and alert systems utilized in a variety of ACOs. In addition, an examination of different data mining procedures used within different electronic health record platforms would prove useful to ACOs looking to improve the care of not only the subpopulations with specific metrics associated with them, but their patient population as a whole. The authors also highlight the need for additional research on health information exchanges, including the cost and resource requirements needed to successfully participate in these types of networks.

Best Practices: Improving Patient Outcomes and Costs in an ACO Through Comprehensive Medication Therapy Management.

BACKGROUND: One of the most important and often overlooked challenges for accountable care organizations (ACOs) is ensuring the optimal use of pharmaceuticals, which can be accomplished by utilizing pharmacists' skillsets and leveraging their full clinical expertise. Developing capabilities that support, monitor, and ensure appropriate medication use, efficacy, and safety is critical to achieving optimal patient outcomes and, ultimately, to an ACO's success. The program described in this article highlights the best practices of Fairview Pharmacy Services' Medication Therapy Management (MTM) program with additional thoughts and considerations on this and similar MTM programs provided by The Working Group on Optimizing Medication Therapy in Value-Based Healthcare. PROGRAM DESCRIPTION: Fairview Pharmacy Services utilizes 23 MTM pharmacists (approximately 18 full-time equivalents) working in 30 locations, who conduct pharmacotherapy workups as part of the MTM services that Fairview provides. Pharmacists focus on patients in a comprehensive manner and assess all of their diseases and medications. Responsibilities include (a) identification of a patient's drug-related needs with a commitment to meet those needs; (b) an assessment and confirmation that all of a patient's drug therapy is appropriately indicated, effective and safe, and that the patient is compliant; (c) achievement of therapy outcomes and ensuring documentation of those outcomes; and (d) collaboration with all members of a patient's care team. OBSERVATIONS: Since 1998, pharmacists have cared for more than 20,000 patients and resolved more than 107,000 medication-related problems which, if left unresolved, could have led to hospital readmissions and emergency visits. Since becoming a Pioneer ACO, Fairview pharmacists have focused on the highest-risk members and have seen over 670 ACO patients, resolving over 2,780 medication-related problems. In terms of clinical outcomes, MTM contributed to optimal care in complex patients with diabetes. A review of 2007 data found that the percentage of diabetes patients optimally managed (as measured by a composite of hemoglobin A1c, low-density lipoprotein, blood pressure, aspirin use, and no smoking) was significantly higher for MTM patients (21% vs. 45%, P less than 0.01). The Fairview MTM also showed a 12:1 return on investment (ROI) when comparing the overall health care costs of patients receiving MTM services with patients who did not receive those services.  IMPLICATIONS: Developing an MTM program to manage and optimize pharmaceuticals will be a cornerstone to managing the health of a population. Important lessons have been learned that may be helpful to other health systems developing MTM programs. In an accountable care environment measuring the return on the investment of all care interventions, including MTM will be essential to maintain the program. The ACO will also have to be able to correctly identify which patients are candidates for MTM services and provide pharmacists with enough autonomy, including scheduling face-to-face interactions with patients and the ability to change prescriptions if necessary, to ensure that timely and effective care is delivered. In order for an ACO to deliver high quality patient-centered medication services, there must be clear lines of communication between providers, pharmacists, and the other care providers within the organization. Finally, a strong and visionary leader is critical to ensuring the success of an MTM program and ultimately the ACO itself. RECOMMENDATIONS: While there is a plethora of literature touting the benefits of either in-person or telephonic-based MTM, there is little research to date that directly compares these 2 MTM delivery types. It is critical for research to address the direct and indirect costs associated with starting and maintaining an MTM program. Information such as technologies required to start a program and length of time until a program breaks even or meets a sufficient ROI can be helpful for health care providers in similar health systems pitching a similar type of program. Finally, there has yet to be significant empirical research into the cost savings of utilizing a pharmacist and MTM services associated with meeting quality and cost benchmarks in an accountable care payment arrangement.

The value of specialty pharmaceuticals - a systematic review.

OBJECTIVES: Novel specialty biopharmaceuticals hold promise for patients living with complex and chronic conditions. However, high research and development costs, special handling, and other necessary enhancements to patient support programs all contribute to frequently higher prices for these products. This study sought to assess the value of specialty pharmaceuticals through an examination of the clinical, functional, and economic benefits of these treatments for the top 3 disease areas by pharmaceutical spend: rheumatoid arthritis (RA), multiple sclerosis (MS), and breast cancer (BC). STUDY DESIGN: Systematic literature review. METHODS: A systematic review of market research and cost-effectiveness articles was conducted for each disease area to assess clinical, functional, and economic outcomes associated with specialty medicine treatments versus the previous standard of care. RESULTS: All RA clinical (American College of Rheumatology) and functional (Health Assessment Questionnaire) outcome articles were classified as positive. The median cost-effectiveness ratio was $38,900 per quality-adjusted life year (QALY). All MS clinical outcome (relapse rate) articles were positive. The MS functional outcome (Expanded Disability Status Scale) findings were less conclusive. The median cost-effectiveness ratio was $248,000 per QALY. The majority of BC articles yielded statistically inconclusive results for survival. All functional outcome (Quality of Life Questionnaire- Core 30) articles were positive. The median cost-effectiveness ratio was $51,900 per QALY. CONCLUSIONS: Novel specialty therapies hold promise for arresting disease progression and improving quality of life for the 3 conditions associated with the highest specialty pharmaceutical spend. These findings demonstrate a strong value proposition for specialty pharmaceuticals, and suggest even greater potential individual patient benefit with consideration of patient heterogeneity.

Are ACOs ready to be accountable for medication use?

BACKGROUND: Accountable care organizations (ACOs) have the potential to lower costs and improve quality through incentives and coordinated care. However, the design brings with it many new challenges. One such challenge is the optimal use of pharmaceuticals. Most ACOs have not yet focused on this integral facet of care, even though medications are a critical component to achieving the lower costs and improved quality that are anticipated with this new model. OBJECTIVE: To evaluate whether ACOs are prepared to maximize the value of medications for achieving quality benchmarks and cost offsets. METHODS: During the fall of 2012, an electronic readiness self-assessment was developed using a portion of the questions and question methodology from the National Survey of Accountable Care Organizations, along with original questions developed by the authors. The assessment was tested and subsequently revised based on feedback from pilot testing with 5 ACO representatives. The revised assessment was distributed via e-mail to a convenience sample (n=175) of ACO members of the American Medical Group Association, Brookings-Dartmouth ACO Learning Network, and Premier Healthcare Alliance. RESULTS: The self-assessment was completed by 46 ACO representatives (26% response rate). ACOs reported high readiness to manage medications in a few areas, such as transmitting prescriptions electronically (70%), being able to integrate medical and pharmacy data into a single database (54%), and having a formulary in place that encourages generic use when appropriate (50%). However, many areas have substantial room for improvement with few ACOs reporting high readiness. Some notable areas include being able to quantify the cost offsets and hence demonstrate the value of appropriate medication use (7%), notifying a physician when a prescription has been filled (9%), having protocols in place to avoid medication duplication and polypharmacy (17%), and having quality metrics in place for a broad diversity of conditions (22%). CONCLUSIONS: Developing the capabilities to support, monitor, and ensure appropriate medication use will be critical to achieve optimal patient outcomes and ACO success. The ACOs surveyed have embarked upon an important journey towards this goal, but critical gaps remain before they can become fully accountable. While many of these organizations have begun adopting health information technologies that allow them to maximize the value of medications for achieving quality outcomes and cost offsets, a significant lag was identified in their inability to use these technologies to their full capacities. In order to provide further guidance, the authors have begun documenting case studies for public release that would provide ACOs with examples of how certain medication issues have been addressed by ACOs or relevant organizations. The authors hope that these case studies will help ACOs optimize the value of pharmaceuticals and achieve the "triple aim" of improving care, health, and cost.

Best practices: improving patient outcomes and costs in an ACO through comprehensive medication therapy management.

BACKGROUND: One of the most important and often overlooked challenges for accountable care organizations (ACOs) is ensuring the optimal use of pharmaceuticals, which can be accomplished by utilizing pharmacists' skillsets and leveraging their full clinical expertise. Developing capabilities that support, monitor, and ensure appropriate medication use, efficacy, and safety is critical to achieving optimal patient outcomes and, ultimately, to an ACO's success. The program described in this article highlights the best practices of Fairview Pharmacy Services' Medication Therapy Management (MTM) program with additional thoughts and considerations on this and similar MTM programs provided by The Working Group on Optimizing Medication Therapy in Value-Based Healthcare. PROGRAM DESCRIPTION: Fairview Pharmacy Services utilizes 23 MTM pharmacists (approximately 18 full-time equivalents) working in 30 locations, who conduct pharmacotherapy workups as part of the MTM services that Fairview provides. Pharmacists focus on patients in a comprehensive manner and assess all of their diseases and medications. Responsibilities include (a) identification of a patient's drug-related needs with a commitment to meet those needs; (b) an assessment and confirmation that all of a patient's drug therapy is appropriately indicated, effective and safe, and that the patient is compliant; (c) achievement of therapy outcomes and ensuring documentation of those outcomes; and (d) collaboration with all members of a patient's care team. OBSERVATIONS: Since 1998, pharmacists have cared for more than 20,000 patients and resolved more than 107,000 medication-related problems which, if left unresolved, could have led to hospital readmissions and emergency visits. Since becoming a Pioneer ACO, Fairview pharmacists have focused on the highest-risk members and have seen over 670 ACO patients, resolving over 2,780 medication-related problems. In terms of clinical outcomes, MTM contributed to optimal care in complex patients with diabetes. A review of 2007 data found that the percentage of diabetes patients optimally managed (as measured by a composite of hemoglobin A1c, low-density lipoprotein, blood pressure, aspirin use, and no smoking) was significantly higher for MTM patients (21% vs. 45%, P < 0.01). The Fairview MTM also showed a 12:1 return on investment (ROI) when comparing the overall health care costs of patients receiving MTM services with patients who did not receive those services. IMPLICATIONS: Developing an MTM program to manage and optimize pharmaceuticals will be a cornerstone to managing the health of a population. Important lessons have been learned that may be helpful to other health systems developing MTM programs. In an accountable care environment measuring the return on the investment of all care interventions, including MTM will be essential to maintain the program. The ACO will also have to be able to correctly identify which patients are candidates for MTM services and provide pharmacists with enough autonomy, including scheduling face-to-face interactions with patients and the ability to change prescriptions if necessary, to ensure that timely and effective care is delivered. In order for an ACO to deliver high quality patient-centered medication services, there must be clear lines of communication between providers, pharmacists, and the other care providers within the organization. Finally, a strong and visionary leader is critical to ensuring the success of an MTM program and ultimately the ACO itself. RECOMMENDATIONS: While there is a plethora of literature touting the benefits of either in-person or telephonic-based MTM, there is little research to date that directly compares these 2 MTM delivery types. It is critical for research to address the direct and indirect costs associated with starting and maintaining an MTM program. Information such as technologies required to start a program and length of time until a program breaks even or meets a sufficient ROI can be helpful for health care providers in similar health systems pitching a similar type of program. Finally, there has yet to be significant empirical research into the cost savings of utilizing a pharmacist and MTM services associated with meeting quality and cost benchmarks in an accountable care payment arrangement.

Introduction: the Interdisciplinary Nursing Quality Research Initiative.

BACKGROUND: The Robert Wood Johnson Foundation launched the Interdisciplinary Nursing Quality Research Initiative (INQRI) program in 2005 to generate, disseminate, and translate research to understand how nurses contribute to and can improve patient care quality. This special edition of Medical Care provides an overview of the program's strategy, goals, and impact, highlighting cross-cutting issues addressed by the initiative. METHODS: INQRI's leadership and select grantees discuss the implications of a collection of studies on the following: advances in the science of nursing's contribution to quality, measurement of quality, interdisciplinary collaboration, implementation methodology, dissemination and translation of findings, and the business case for nursing. RESULTS: A comprehensive review of the scholarly literature published in 2004 and 2009 found that the evidence linking nursing to quality of care has grown. The second paper discusses INQRI's work on measurement of quality of care, revealing the need for additional comprehensive measures. The third paper examines INQRI's focus on interdisciplinary collaboration, finding that it can enhance methodological approaches and result in substantive changes in health delivery systems. The fourth paper presents methodological challenges faced in health care implementation, emphasizing the need for standardized terms and research designs. The fifth paper addresses INQRI's commitment to translating research into practice, illustrating dissemination strategies and lessons learned. The final paper discusses how the INQRI program has contributed to the current evidence regarding the business case for nursing. DISCUSSION: This supplement describes the accomplishments of the INQRI program, discusses current issues in research design and implementation, and places INQRI research within the larger context regarding advances in nursing science.

Linkages between nursing and the quality of patient care: a 2-year comparison.

BACKGROUND: In 2005, the Robert Wood Johnson Foundation established the Interdisciplinary Nursing Quality Research Initiative (INQRI) program to produce rigorous evidence regarding linkages between nursing and quality of health care. The purpose of this paper is to describe scientific advances in understanding relationships between nursing, care processes, and the outcomes of the people supported by this discipline in 2004 (year before INQRI's launch) and in 2009 (5 years after INQRI was established). METHODS: Comprehensive literature reviews for the years 2004 and 2009 were conducted using a conceptually based search strategy and multidisciplinary engines. The designs, methods, results, and conclusions of included papers were summarized, synthesized, and analyzed. RESULTS: The literature search identified 389 studies (161 in 2004; 228 in 2009), which examined the relationship between nursing and patient care quality. The number of published papers in all categories of study designs-nonexperimental (72 in 2004; 97 in 2009), quasi-experimental (55 in 2004; 80 in 2009) and experimental (34 in 2004; 51 in 2009)-increased between the years 2004 and 2009. This line of inquiry also has expanded its reach through publications in a greater diversity of journals and journals with higher impact ratings. DISCUSSION: The body of evidence regarding linkages between nursing and quality of care has increased in the nature and depth of science between 2004 and 2009, as seen in higher rates and quality of publications, enhanced methodological rigor, and evidence of stronger interdisciplinary collaboration. Although the unique contribution of INQRI to this expanded body of knowledge is unclear, the evidence supports the increased importance of INQRI's goal of measuring and enhancing nursing's contributions to the quality of patient care.

Secondary hyperalgesia in the postoperative pain model is dependent on spinal calcium/calmodulin-dependent protein kinase II alpha activation.

BACKGROUND: Spinally administered non-N-methyl-D-aspartate (NMDA), but not NMDA, receptor antagonists block primary (1 degree) and secondary (2 degrees) mechanical hyperalgesia and spontaneous pain after plantar incision. Hyperalgesia after thermal stimulation is also mediated by non-NMDA, but not NMDA, receptors. Although previous pain behavior studies in the thermal stimulus model demonstrated distinct protein kinase involvement downstream from spinal non-NMDA receptor activation, protein kinase signaling mechanisms have not been examined in the postoperative pain model. In the present study, we investigated whether spinal calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) mediates 1 degree and/or 2 degrees hyperalgesia and spontaneous pain behavior after plantar incision. METHODS: Catheterized rats received a 1 cm incision in the hindpaw and were tested over 2 days for responses to mechanical stimulation adjacent to or 1 cm away from the incision site. Some rats received intrathecal (IT) pretreatment with a CaMKIIalpha inhibitor (14, 34, or 104 nmol KN-93) or vehicle (5% dimethyl sulfoxide in sterile saline). Separate groups received IT 34 nmol or 104 nmol KN-93 and were tested for hindpaw weight bearing. Lumbar spinal cords were extracted 1 h after incision or sham treatment to measure phosphorylated CaMKIIalpha and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid GLUR1-831 in Western immunoblots. RESULTS: Incision increased spinal CaMKIIalpha and GLUR1-831 phosphorylation. Although pretreatment with all doses of IT KN-93 reduced the development of 2 degrees hyperalgesia, only 34 nmol KN-93 appeared to have an effect on 1 degrees hyperalgesia. IT KN-93 did not affect nonevoked pain. CONCLUSION: Spinal sensitization underlying incision-evoked hyperalgesia involves spinal CaMKIIalpha activation and enhanced spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor (AMPA) function.