Pain hypersensitivity and spinal nociceptive hypersensitivity in chronic pain: prevalence and associated factors.

Hypersensitivity of pain pathways is considered a relevant determinant of symptoms in chronic pain patients, but data on its prevalence are very limited. To our knowledge, no data on the prevalence of spinal nociceptive hypersensitivity are available. We studied the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity in 961 consecutive patients with various chronic pain conditions. Pain threshold and nociceptive withdrawal reflex threshold to electrical stimulation were used to assess pain hypersensitivity and spinal nociceptive hypersensitivity, respectively. Using 10th percentile cutoff of previously determined reference values, the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity (95% confidence interval) was 71.2 (68.3-74.0) and 80.0 (77.0-82.6), respectively. As a secondary aim, we analyzed demographic, psychosocial, and clinical characteristics as factors potentially associated with pain hypersensitivity and spinal nociceptive hypersensitivity using logistic regression models. Both hypersensitivity parameters were unaffected by most factors analyzed. Depression, catastrophizing, pain-related sleep interference, and average pain intensity were significantly associated with hypersensitivity. However, none of them was significant for both unadjusted and adjusted analyses. Furthermore, the odds ratios were very low, indicating modest quantitative impact. To our knowledge, this is the largest prevalence study on central hypersensitivity and the first one on the prevalence of spinal nociceptive hypersensitivity in chronic pain patients. The results revealed an impressively high prevalence, supporting a high clinical relevance of this phenomenon. Electrical pain thresholds and nociceptive withdrawal reflex explore aspects of pain processing that are mostly independent of sociodemographic, psychological, and clinical pain-related characteristics.

A follow-up on Acute Pain Services in Germany compared to international survey data.

BACKGROUND After the introduction of instruments for benchmarking, certification and a national guideline for acute pain management, the aim of this study was to describe the current structure, processes and quality of German acute pain services (APS). METHODS All directors of German departments of anaesthesiology were invited to complete a postal questionnaire on structures und processes of acute pain management. The survey asked for staff, techniques and quality criteria, which enabled a comparison to previous data from 1999 and surveys from other countries. RESULTS Four hundred and eight (46%) questionnaires were returned. APS have increased considerably and are now available in 81% of the hospitals, mainly anaesthesia based. However, only 45% fulfilled the minimum quality criteria, such as the assignment of personnel, the organization of patient care during nights and weekends, written protocols for postoperative pain management, regular assessments and documenting pain scores. Staff resources varied considerably, but increased compared to 1999. Two daily rounds were performed in 71%, either by physicians and nurses (42%), by physicians only (25%) or by supervised nurses (31%). Most personnel assigned to the APS shared this work along with other duties. Only 53% of the hospitals had an integrated rotation for training their specialty trainees. CONCLUSIONS The availability of APS in Germany and other countries has increased over the last decade; however, the quality of nearly half of the APS is questionable. Against the disillusioning background of recently reported unfavourable pain-related patient outcomes, the structures, organization and quality of APS should be revisited.

Non-surgical treatment of pain associated with posterior tibial tendon dysfunction: study protocol for a randomised clinical trial

BACKGROUND Symptoms associated with pes planovalgus or flatfeet occur frequently, even though some people with a flatfoot deformity remain asymptomatic. Pes planovalgus is proposed to be associated with foot/ankle pain and poor function. Concurrently, the multifactorial weakness of the tibialis posterior muscle and its tendon can lead to a flattening of the longitudinal arch of the foot. Those affected can experience functional impairment and pain. Less severe cases at an early stage are eligible for non-surgical treatment and foot orthoses are considered to be the first line approach. Furthermore, strengthening of arch and ankle stabilising muscles are thought to contribute to active compensation of the deformity leading to stress relief of soft tissue structures. There is only limited evidence concerning the numerous therapy approaches, and so far, no data are available showing functional benefits that accompany these interventions. METHODS After clinical diagnosis and clarification of inclusion criteria (e.g., age 40-70, current complaint of foot and ankle pain more than three months, posterior tibial tendon dysfunction stage I & II, longitudinal arch flattening verified by radiography), sixty participants with posterior tibial tendon dysfunction associated complaints will be included in the study and will be randomly assigned to one of three different intervention groups: (i) foot orthoses only (FOO), (ii) foot orthoses and eccentric exercise (FOE), or (iii) sham foot orthoses only (FOS). Participants in the FOO and FOE groups will be allocated individualised foot orthoses, the latter combined with eccentric exercise for ankle stabilisation and strengthening of the tibialis posterior muscle. Participants in the FOS group will be allocated sham foot orthoses only. During the intervention period of 12 weeks, all participants will be encouraged to follow an educational program for dosed foot load management (e.g., to stop activity if they experience increasing pain). Functional impairment will be evaluated pre- and post-intervention by the Foot Function Index. Further outcome measures include the Pain Disability Index, Visual Analogue Scale for pain, SF-12, kinematic data from 3D-movement analysis and neuromuscular activity during level and downstairs walking. Measuring outcomes pre- and post-intervention will allow the calculation of intervention effects by 3×3 Analysis of Variance (ANOVA) with repeated measures. DISCUSSION The purpose of this randomised trial is to evaluate the therapeutic benefit of three different non-surgical treatment regimens in participants with posterior tibial tendon dysfunction and accompanying pes planovalgus. Furthermore, the analysis of changes in gait mechanics and neuromuscular control will contribute to an enhanced understanding of functional changes and eventually optimise conservative management strategies for these patients. TRIAL REGISTRATION ClinicalTrials.gov Protocol Registration System: ClinicalTrials.gov ID NCT01839669.

Factors Related to Mental Health of Native Americans in Eastern Tribes

This paper is part of a five-year research project funded by the National Institute on Disability and Rehabilitation Research (NIDRR) that addresses the health, disability and service needs of Native Americans in eastern tribes. The Participatory Action Research model with a community-based approach was used to facilitate collaboration among the participating tribes. Native American research technicians conducted individual interviews with members of their tribes. Demographics, prevalence of disabilities, and various factors associated with health and mental health are presented. Of the 858 tribal members who responded to survey questions, the third most prominent health problem reported was mental illness.

Back pain in migrant farmworker families and farmworker high school students from Starr County, Texas

Back symptoms are a major global public health problem with the lifetime prevalence ranging between 50-80%. Research suggests that work-related factors contribute to the occurrence of back pain in various industries. Despite the hazardous nature, strenuous tasks, and awkward postures associated with farm work, little is known about back injury and symptoms in farmworker adults and children. Research in the United States is particularly limited. This is a concern given the large proportion of migrant farmworkers in the United States without adequate access to healthcare as well as a substantial number of youth working in agriculture. The present study describes back symptoms and identifies work-related factors associated with back pain in migrant farmworker families and farmworker high school students from Starr County, TX. Two separate datasets were used from two cohort studies "Injury and Illness Surveillance in Migrant Farmworkers (MANOS)" (study A: n=267 families) and "South Texas Adolescent Rural Research Study (STARRS)" (study B: n=345). Descriptive and inferential statistics including multivariable logistic regression were used to identify work-related factors associated with back pain in each study. In migrant farmworker families, the prevalence of chronic back pain during the last migration season ranged from 9.5% among youngest children to 33.3% among mothers. Chronic back pain was significantly associated with increasing age; fairly bad/very bad quality of sleep while migrating; fewer than eight hours of sleep at home in Starr County, TX; depressive symptoms while migrating; self-provided water for washing hands/drinking; weeding at work; and exposure to pesticide drift/direct spray. Among farmworker adolescents, the prevalence of severe back symptoms was 15.7%. Severe back symptoms were significantly associated with being female; history of a prior accident/back injury; feeling tense, stressed, or anxious sometimes/often; lifting/carrying heavy objects not at work; current tobacco use; increasing lifetime number of migrant farmworker years; working with/around knives; and working on corn crops. Overall, results support that associations between work-related exposures and chronic back pain and severe back symptoms remain after controlling for the effect of non-work exposures in farmworker populations. ^

Blood-oxygen-level-dependent (BOLD) signal changes in total cortex and subcortex, pain, reward, and vigilance regions during mechanical pressure pain after morphine administration

Morphine is the most common clinical choice in the management of severe pain. Although the molecular mechanisms of morphine have already been characterized, the cerebral circuits by which it attenuates the sensation of pain have not yet been studied in humans. The objective of this two-arm (morphine versus placebo), between-subjects study was to examine whether morphine affects pain via pain-related cortical circuits, but also via reward regions that relate to the motivational state, as well as prefrontal regions that relate to vigilance as a result of morphine's sedative effects. Cortical activity was measured by the blood-oxygen-level-dependent (BOLD) signal changes using functional magnetic resonance imaging (fMRI). ^ The novelty of this study is at three levels: (i) to develop a methodology that will assess the average BOLD signal across subjects for the pain, reward, and vigilance cortical systems; (ii) to examine whether the reward and/or sedative effects of morphine are contributing factors to cortical regions associated with the motivational state and vigilance; and (iii) to propose a neuroanatomical model related to the opioid-sensitive effects of reward and sedation as a function of cortical activity related to pain in an effort to assess future analgesics. ^ Consistent with our hypotheses, our findings showed that the decrease in total pain-related volume activated between the post- and the pre-treatment morphine group was about 78%, while the post-treatment placebo group displayed only a 5% decrease when compared to pre-treatment levels of activation. The volume increase in reward regions was 451% in the post-treatment compared to the pre-treatment morphine condition. Finally, the volumetric decrease in vigilance regions was 63% in the posttreatment compared to the pre-treatment morphine condition. ^ These findings imply that changes in the blood flow of the reward and vigilance regions may be contributing factors in producing the analgesic effect under morphine administration. Future studies need to replicate this study in a higher resolution fMRI environment and to assess the proposed neuroanatomical model in patient populations. The necessity of pain research is apparent, since pain cuts across different diseases especially chronic ones, and thus, is recognized as a vital public health developing area. ^

The impact of antibiotic associated diarrhea on health related quality of life in hospitalized patients

Objective. To determine the impact of antibiotic associated diarrhea (AAD) on health related quality of life (HRQOL) in hospitalized patients compared to matched controls without diarrhea. ^ Methods. This is a hospital-based, matched case-control study using secondary data from a prospective cohort trial of patients receiving broad-spectrum antibiotics. One hundred and seventy-eight patients were recruited of whom 18 (10%) reported having antibiotic associated diarrhea. Two non-diarrhea controls were selected for each case with diarrhea giving a final sample of 18 cases and 36 controls. Responses from Short Form (SF) 36 questionnaire were aggregated into eight domains including physical functioning (PF), role-functioning physical (RP), bodily pain (BP), general health (GH), social functioning (SF), vitality (VT), role-functioning emotional (RE), and mental health (MH). The eight domains were compared between cases and controls. A GI targeted HRQOL measure was administered to 13 patients with AAD. Responses from the disease-specific instrument were combined in eight subscale scores: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sex, and relationships. ^ Results. The sample consisted of 41 females (75.9%) and 13 males (24.1%) aged 53.5 ± 14.4 years (range: 21-76 years). Twenty five patients (46%) were Caucasian, 15 (27%) were African American, 13(24%) were Hispanic and 1(2%) was Asian. In univariate analysis, no significant differences in quality of life outcomes were observed in each of the SF36 domains between the case patients and matched controls. There were trends for decreased scores on the role-functioning physical, bodily pain, general health, social functioning, mental health, and mental summary domains. In total, 7 of 8 domain scores were lower in patients with AAD and 5 of 8 domain scores were lower by more than 5 points (considered clinically significant). Controlling for age, patients with antibiotic associated diarrhea had significantly lower general health, vitality, and mental health scale scores (p<0.05 each). The disease-specific scores were significantly lower in patients with AAD than those in published norms for irritable bowel syndrome patients. ^ Conclusion. In this small sample, several areas of decreased QOL in patients with AAD compared to matched controls were noted. A larger sample size to validate these results is necessary.^

Frequency, severity and distress of dialysis-related symptoms reported by patients on hemodialysis

Purpose. To determine which symptoms are the most reported, occur most frequently, have the greatest severity, and cause the most bother for hemodialysis (HD) patients and to determine if the symptoms experienced differ between the first (HD 1) and second (HD 2) treatments of the week. ^ Design. An observational, comparative design was used to determine participants' HD symptoms experience on HD 1 and HD 2, and the effect of the symptom experience on Quality of Life (QOL). One hundred subjects were recruited from five dialysis centers. ^ Methods. The adapted Dialysis Frequency, Severity and Symptom Burden Index (DFSSBI) and the Medical Outcomes Study Short Form 36 (MOS SF 36) were administered (N = 99) on HD 1 and the DFSSBI again on HD 2. Data were analyzed for significance among symptoms experience test scores in relation to HD 1 and HD 2, QOL, and gender and age. ^ Results. Of 31 symptoms assessed, respondents reported an average of 9.69 symptoms on HD 1 and 7.51 symptoms on HD 2. Overall, more symptoms were reported, and were more frequent, severe and bothersome on HD 1 when the level of metabolic waste is highest. The most reported symptoms included tiredness, dry skin, difficulty falling asleep, itching, numbness/tingling, difficulty staying asleep, decreased interest in sex, and bone/joint pain. Females scored consistently higher than males in the four symptom dimensions. The respondents reported about the same as the population norm (50) on the physical component summary score of the MOS SF 36 and higher than the norm (65.23) on the mental component summary score. ^ Conclusion. The study findings highlighted the fact that hemodialysis patients experience multiple symptoms that can be frequent, severe, and bothersome. Interventions should be developed and tested to reduce symptom burden and improve QOL. ^

Process to develop a State Model Law to reduce prescription drug trafficking while protecting pain management

This paper will discuss the intersection of pill mills and the under-treatment of pain, while addressing the unintended consequence that cracking down on pill mills actually has on medical professionals' treatment of legitimate pain in clinical settings. Moreover, the impact each issue has on the spectrum of related policy, regulatory issues and legislation will be analyzed while addressing the national impact on medical care. Lastly, this paper will outline a process to develop a State Model Law on this subject. This process will include suggestions for the future and how we can move forward to adequately address public safety needs and how we can attempt to mitigate the unintended impact prescription drug trafficking has had on a patient's right to appropriate pain management. This balance is achievable and this paper will address ways we can find this elusive balancing point through the development of a State Model Law. ^

A methodologic study of pain assessment in Anglo and Hispanic children with cancer

There is growing clinical evidence that even young children experience pain and accompanying anxiety. Few instruments have been validated to assess pain characteristics in children. The study of related demographic, illness, psychologic and parental factors in children has also been limited. This study examines the reliability and validity of pain assessment tools in an outpatient pediatric cancer population. A total of 78 children from three to fifteen years of age were observed and interviewed about the pain of invasive procedures. The effect of cultural factors and the stress of acculturation were examined by comparing data from two cultural groups, Anglo and Hispanic.^ Spielberger State-Trait Anxiety Scales were administered to children and parents prior to an invasive procedure. The Procedure Behavioral Checklist (PBCL) was used for observation of the child's response during the procedure. The Children's Procedural Interview (CPI) which contains items on the PBCL and visual analogues (scales of faces indicating varying degrees of pain and anxiety) was administered following the procedure.^ Reliability coefficients for Anglos were.78 on the PBCL,.79 on the CPI and.85 on the visual analogue scales. For Hispanics, the reliability for the PBCL was.54, while the CPI had a reliability of.72 and the visual analogue scales,.87. Construct validity was demonstrated by high correlations between the PBCL and CPI scores for both ethnic groups (.66 for Anglos and.64 for Hispanics) and by the significant correlation of State anxiety scores with both PBCL and CPI scores. Age was inversely correlated with PBCL and CPI scores for both ethnic groups. Hispanic parents' anxiety scores were higher than Anglo parents, but were not highly correlated with their child's PBCL, CPI or State-Trait anxiety scores. Caregivers' ratings were correlated with the PBCL scores for Anglos but not for Hispanics.^ The findings of this study indicate that pain responses may be reliably assessed using both observational and self-report methods in children, though differences in Anglo and Hispanic cultures exist. Differences in pain symptomatology and assessment in the two cultural groups warrant further study. ^

Infrared thermography and shoulder pain in wheelchair users = Termografía infrarroja y dolor de hombro en usuarios de sillas de ruedas

Las personas que usan la silla de ruedas como su forma de movilidad prioritaria presentan una elevada incidencia (73%) de dolor de hombro debido al sobreuso y al movimiento repetitivo de la propulsión. Existen numerosos métodos de diagnóstico para la detección de las patologías del hombro, sin embargo la literatura reclama la necesidad de un test no invasivo y fiable, y sugiere la termografía como una técnica adecuada para evaluar el dolor articular. La termografía infrarroja (IRT) proporciona información acerca de los procesos fisiológicos a través del estudio de las distribuciones de la temperatura de la piel. Debido a la alta correlación entre ambos lados corporales, las asimetrías térmicas entre flancos contralaterales son una buena indicación de patologías o disfunciones físicas subyacentes. La fiabilidad de la IRT ha sido estudiada con anterioridad en sujetos sanos, pero nunca en usuarios de sillas de ruedas. Las características especiales de la población con discapacidad (problemas de sudoración y termorregulación, distribución sanguínea o medicación), hacen necesario estudiar los factores que afectan a la aplicación de la IRT en usuarios de sillas de ruedas. La bibliografía discrepa en cuanto a los beneficios o daños resultantes de la práctica de la actividad física en las lesiones de hombro por sobreuso en usuarios de sillas de ruedas. Recientes resultados apuntan a un aumento del riesgo de rotura del manguito rotador en personas con paraplejia que practican deportes con elevación del brazo por encima de la cabeza. Debido a esta falta de acuerdo en la literatura, surge la necesidad de analizar el perfil termográfico en usuarios de sillas de ruedas sedentarios y deportistas y su relación con el dolor de hombro. Hasta la fecha sólo se han publicado estudios termográficos durante el ejercicio en sujetos sanos. Un mayor entendimiento de la respuesta termográfica al ejercicio en silla de ruedas en relación al dolor de hombro clarificará su aparición y desarrollo y permitirá una apropiada intervención. El primer estudio demuestra que la fiabilidad de la IRT en usuarios de sillas de ruedas varía dependiendo de las zonas analizadas, y corrobora que la IRT es una técnica no invasiva, de no contacto, que permite medir la temperatura de la piel, y con la cual avanzar en la investigación en usuarios de sillas de ruedas. El segundo estudio proporciona un perfil de temperatura para usuarios de sillas de ruedas. Los sujetos no deportistas presentaron mayores asimetrías entre lados corporales que los sedentarios, y ambos obtuvieron superiores asimetrías que los sujetos sin discapacidad reportados en la literatura. Los no deportistas también presentaron resultados más elevados en el cuestionario de dolor de hombro. El área con mayores asimetrías térmicas fue hombro. En deportistas, algunas regiones de interés (ROIs) se relacionaron con el dolor de hombro. Estos resultados ayudan a entender el mapa térmico en usuarios de sillas de ruedas. El último estudio referente a la evaluación de la temperatura de la piel en usuarios de sillas de ruedas en ejercicio, reportó diferencias significativas entre la temperatura de la piel antes del test y 10 minutos después del test de propulsión de silla de ruedas, en 12 ROIs; y entre el post-test y 10 minutos después del test en la mayoría de las ROIs. Estas diferencias se vieron atenuadas cuando se compararon las asimetrías antes y después del test. La temperatura de la piel tendió a disminuir inmediatamente después completar el ejercicio, e incrementar significativamente 10 minutos después. El análisis de las asimetrías vs dolor de hombro reveló relaciones significativas negativas en 5 de las 26 ROIs. No se encontraron correlaciones significativas entre las variables de propulsión y el cuestionario de dolor de hombro. Todas las variables cinemáticas correlacionaron significativamente con las asimetrías en múltiples ROIs. Estos resultados indican que los deportistas en sillas de ruedas exhiben una capacidad similar de producir calor que los deportistas sin discapacidad; no obstante, su patrón térmico es más característico de ejercicios prolongados que de esfuerzos breves. Este trabajo contribuye al conocimiento de la termorregulación en usuarios de sillas de ruedas durante el ejercicio, y aporta información relevante para programas deportivos y de rehabilitación. ABSTRACT Individuals who use wheelchairs as their main means of mobility have a high incidence (73%) of shoulder pain (SP) owing to overuse and repetitive propulsion movement. There are numerous diagnostic methods for the detection of shoulder pathologies, however the literature claims that a noninvasive accurate test to properly assess shoulder pain would be necessary, and suggests thermography as a suitable technique for joint pain evaluation. Infrared thermography (IRT) provides information about physiological processes by studying the skin temperature (Tsk) distributions. Due to the high correlation of skin temperature between both sides of the body, thermal asymmetries between contralateral flanks are an indicator of underlying pathologies or physical dysfunctions. The reliability of infrared thermography has been studied in healthy subjects but there are no studies that have analyzed the reliability of IRT in wheelchair users (WCUs). The special characteristics of people with disabilities (sweating and thermoregulation problems, or blood distribution) make it necessary to study the factors affecting the application of IRT in WCUs. Discrepant reports exist on the benefits of, or damage resulting from, physical exercise and the relationship to shoulder overuse injuries in WCUs. Recent findings have found that overhead sports increase the risk of rotator cuff tears in wheelchair patients with paraplegia. Since there is no agreement in the literature, the thermographic profile of wheelchair athletes and nonathletes and its relation with shoulder pain should also be analysed. Infrared thermographic studies during exercise have been carried out only with able-bodied population at present. The understanding of the thermographic response to wheelchair exercise in relation to shoulder pain will offer an insight into the development of shoulder pain, which is necessary for appropriate interventions. The first study presented in this thesis demonstrates that the reliability of IRT in WCUs varies depending on the areas of the body that are analyzed. Moreover, it corroborates that IRT is a noninvasive and noncontact technique that allows the measurement of Tsk, which will allow for advances to be made in research concerned with WCUs. The second study provides a thermal profile of WCUs. Nonathletic subjects presented higher side-to-side skin temperature differences (ΔTsk) than athletes, and both had greater ΔTsk than the able-bodied results that have been published in the literature. Nonathletes also revealed larger Wheelchair Users Shoulder Pain Index (WUSPI) score than athletes. The shoulder region of interest (ROI) was the area with the highest ΔTsk of the regions measured. The analysis of the athletes’ Tsk showed that some ROIs are related to shoulder pain. These findings help to understand the thermal map in WCUs. Finally, the third study evaluated the thermal response of WCUs in exercise. There were significant differences in Tsk between the pre-test and the post-10 min in 12 ROIs, and between the post-test and the post-10 in most of the ROIs. These differences were attenuated when the ΔTsk was compared before and after exercise. Skin temperature tended to initially decrease immediately after the test, followed by a significant increase at 10 minutes after completing the exercise. The ΔTsk versus shoulder pain analysis yielded significant inverse relationships in 5 of the 26 ROIs. No significant correlations between propulsion variables and the results of the WUSPI questionnaire were found. All kinematic variables were significantly correlated with the temperature asymmetries in multiple ROIs. These results present indications that high performance wheelchair athletes exhibit similar capacity of heat production to able-bodied population; however, they presented a thermal pattern more characteristic of a prolonged exercise rather than brief exercise. This work contributes to improve the understanding about temperature changes in wheelchair athletes during exercise and provides implications to the sports and rehabilitation programs.

Pain perception: Is there a role for primary somatosensory cortex?

Anatomical, physiological, and lesion data implicate multiple cortical regions in the complex experience of pain. These regions include primary and secondary somatosensory cortices, anterior cingulate cortex, insular cortex, and regions of the frontal cortex. Nevertheless, the role of different cortical areas in pain processing is controversial, particularly that of primary somatosensory cortex (S1). Human brain-imaging studies do not consistently reveal pain-related activation of S1, and older studies of cortical lesions and cortical stimulation in humans did not uncover a clear role of S1 in the pain experience. Whereas studies from a number of laboratories show that S1 is activated during the presentation of noxious stimuli as well as in association with some pathological pain states, others do not report such activation. Several factors may contribute to the different results among studies. First, we have evidence demonstrating that S1 activation is highly modulated by cognitive factors that alter pain perception, including attention and previous experience. Second, the precise somatotopic organization of S1 may lead to small focal activations, which are degraded by sulcal anatomical variability when averaging data across subjects. Third, the probable mixed excitatory and inhibitory effects of nociceptive input to S1 could be disparately represented in different experimental paradigms. Finally, statistical considerations are important in interpreting negative findings in S1. We conclude that, when these factors are taken into account, the bulk of the evidence now strongly supports a prominent and highly modulated role for S1 cortex in the sensory aspects of pain, including localization and discrimination of pain intensity.

The genetic mediation of individual differences in sensitivity to pain and its inhibition

The underlying bases of the considerable interindividual variability in pain-related traits are starting to be revealed. Although the relative importance of genes versus experience in human pain perception remains unclear, rodent populations display large and heritable differences in both nociceptive and analgesic sensitivity. The identification and characterization of particularly divergent populations provides a powerful initial step in the genetic analysis of pain, because these models can be exploited to identify genes contributing to the behavior-level variability. Ultimately, DNA sequence differences representing the differential alleles at pain-relevant genes can be identified. Thus, by using a combination of “top-down” and “bottom-up” strategies, we are now able to genetically dissect even complex biological traits like pain. The present review summarizes the current progress toward these ends in both humans and rodents.

The affective component of pain in rodents: Direct evidence for a contribution of the anterior cingulate cortex

Numerous human and animal studies indirectly implicate neurons in the anterior cingulate cortex (ACC) in the encoding of the affective consequences of nociceptor stimulation. No causal evidence, however, has been put forth linking the ACC specifically to this function. Using a rodent pain assay that combines the hind-paw formalin model with the place-conditioning paradigm, we measured a learned behavior that directly reflects the affective component of pain in the rat (formalin-induced conditioned place avoidance) concomitantly with “acute” formalin-induced nociceptive behaviors (paw lifting, licking, and flinching) that reflect the intensity and localization of the nociceptive stimulus. Destruction of neurons originating from the rostral, but not caudal, ACC reduced formalin-induced conditioned place avoidance without reducing acute pain-related behaviors. These results provide evidence indicating that neurons in the ACC are necessary for the “aversiveness” of nociceptor stimulation.

The genetics of pain and pain inhibition.

The present review summarizes the current state of knowledge about the genetics of pain-related phenomena and illustrates the scope and power of genetic approaches to the study of pain. We focus on work performed in our laboratories in Jastrzebiec, Poland; Portland, OR; and Los Angeles, which we feel demonstrates the continuing usefulness of classical genetic approaches, especially when used in combination with newly available molecular genetic techniques.