Risk Factors and Mechanisms for Persistent Postsurgical Pain After Total Knee Replacement
Condition: Persistent Postsurgical Pain
MeSH terms: Pain, Postoperative
Study type: Observational

Summary: 
      Osteoarthritis (OA) is the single most common cause of disability in mid and late life. About
      27 million people in the United States suffer from this incurable process and 10 million have
      OA of the knee. Total knee replacement (TKR) is a reliable treatment option for patients
      disabled by knee OA who have failed non-operative treatment; 58% of these surgeries are
      performed on patients 65 years or older. Despite the overall success of TKR in most cases,
      persistent postsurgical pain (PPP) of the operated knee remains a common and often difficult
      to treat postoperative outcome affecting 13-20% of all patients at 6 months post-TKR, which
      amounts to 65,000-100,000 patients/year in the USA. Important secondary outcomes of PPP are
      restricted physical mobility and poor quality of life, especially in older patients.

      Recent findings spanning the pre-, intra- and postoperative periods suggest that the
      development of PPP after TKR is a multi-factorial process, comprised of both neurophysiologic
      and psychosocial factors. Likely determinates include preoperative thermal pain sensitivity,
      anxiety, pain catastrophizing; and postoperative area of secondary mechanical hyperalgesia or
      hypoalgesia (numbness). There is already agreement that the intensity of early (acute)
      postoperative pain is one of the factors predicting PPP. To date, most studies have examined
      the role of risk factors in isolation and/or within a single domain, and no prospective study
      has comprehensively evaluated the interaction of neurophysiologic and psychosocial variables
      in the evolution of PPP following TKR. The lack of information regarding how neurophysiologic
      pathways and patient cognitive/affective states interact over time following otherwise
      successful TKR has greatly undermined the understanding of PPP after TKR.

      The proposed project is a single-site, prospective study of 300 OA patients aged 18-85 yrs
      undergoing primary TKR. The study is designed to identify factors from the pre-, intra- and
      postoperative phases of TKR that contribute to PPP at 6 months. Specific risk factors were
      selected because they are potentially modifiable, and therefore may be amenable to
      intervention. Patients will be assessed from pre-surgery to 6 months post surgery. The
      proposed multi-factorial and prospective approach to investigating risk factors is a vital
      next step towards understanding the complex phenomenon of PPP.
    

Detailed description: 
      Overall Strategy: The primary aim of this application is to investigate relationships of risk
      factors to the development of persistent postoperative pain (PPP) at 6 mo following TKR,
      through independently predictive and mediated models.

      These risk factors are preoperative thermal pain sensitivity, pain anxiety and
      catastrophizing; postoperative area of secondary mechanical hyperalgesia or hypoalgesia
      (numbness) and pain intensity. PPP for this study will be defined as "pain in the operated
      knee at six months after TKR, with other causes of pain excluded and reported intensity on
      0-10 Numerical Response Scale (NRS) scale of ≥4". The study will also evaluate the
      relationship of PPP incidence with the severity of functional impairment. This is a
      single-site prospective clinical investigation of 300 consented OA patients undergoing
      primary, unilateral TKR.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Osteoarthritis patients at the RUSH university medical center undergoing primary,
        unilateral TKR
      
Biospecimen description: 
      DNA, RNA
    
Keywords: persistent postsurgical pain (PPP)