Case Report on Sickle Cell Anemia

Introduction: Sickle cell anemia is a kind of anemia caused by a virus a homozygous HbS mutation (HbSS). Sickle cell disease (SCD) is a congenital blood illness that has an impact children. It is inherited from a parent’s DNA. SCD patients produce an abnormal kind of hemoglobin. This is the oxygen-transporting protein found in red blood cells. SCD causes a lack of oxygen in organs and tissues of the body. Clinical Findings: Fever, Cough and cold, pain in lower extremities, Bodyache , Fatigue and Anemia (6.3 gm/). Diagnostic Evaluation: Blood test: Hb -6.3gm%, Total RBC count -2.2millions/cu mm, RDW- 18.2%, HCT-20.2%, Total WBC count 3000/cu mm, Monocytes 02%, Granulocytes 20%, Lymphocytes 77%, AST(SGOT) – 110 UL. Peripheral Smear: RBC mild hypochromic with mild cytosis which show few microcytic and mildly Hypochromic. Platelets – Reduced on smear, APC -60,000 cells. Ultrasonography: Splenomegaly. Therapeutic Interventions: Blood transfusion, Inj. Cefotaxime 750 mg IV x BD, Syr. Azee 4ml x OD, Tab. Folic Acid 5 mg x OD, Tab. Udiliv 150mg x BD, Cap. Hydra 500 mg x OD. Outcome: After treatment, the child show improvement. His fever and body ache, cough and cold fatigue and pain in hands and leg were relieved and his Hb% increased from 6.4 gm% to 11 gm% after blood transfusion. Conclusion: My patient was admitted to Pediatric Ward No- 22 in AVBRH with a known case of SCA kind of anemia a body in which he had complaint fever and body ache, cough and cold fatigue and pain in hands and leg. After getting appropriate treatment his condition was improved.

Pain sensitivity in men who have never experienced a headache: an observer blinded case control study

Background Headache affects 90–99% of the population. Based on the question “Do you think that you never ever in your whole life have had a headache?” 4% of the population say that they have never experienced a headache. The rarity of never having had a headache suggests that distinct biological and environmental factors may be at play. We hypothesized that people who have never experienced a headache had a lower general pain sensitivity than controls. Methods We included 99 male participants, 47 headache free participants and 52 controls, in an observer blinded nested case-control study. We investigated cold pain threshold and heat pain threshold using a standardized quantitative sensory testing protocol, pericranial tenderness with total tenderness score and pain tolerance with the cold pressor test. Differences between the two groups were assessed with the unpaired Student’s t-test or Mann-Whitney U test as appropriate. Results There was no difference in age, weight or mean arterial pressure between headache free participants and controls. We found no difference in pain detection threshold, pericranial tenderness or pain tolerance between headache free participants and controls. Conclusion Our study clearly shows that freedom from headache is not caused by a lower general pain sensitivity. The results support the hypothesis that headache is caused by specific mechanisms, which are present in the primary headache disorders, rather than by a decreased general sensitivity to painful stimuli. Trial registration Registered at ClinicalTrials.gov (NCT04217616), 3rd January 2020, retrospectively registered.

Vasoconstriction Response to Mental Stress in Sickle Cell Disease: The Role of the Cardiac and Vascular Baroreflexes

Recent studies have shown that individuals with sickle cell disease (SCD) exhibit greater vasoconstriction responses to physical autonomic stressors, such as heat pain and cold pain than normal individuals, but this is not the case for mental stress (MTS). We sought to determine whether this anomalous finding for MTS is related to inter-group differences in baseline cardiac and vascular autonomic function. Fifteen subjects with SCD and 15 healthy volunteers participated in three MTS tasks: N-back, Stroop, and pain anticipation (PA). R–R interval (RRI), arterial blood pressure and finger photoplethysmogram (PPG) were continuously monitored before and during these MTS tasks. The magnitude of vasoconstriction was quantified using change in PPG amplitude (PPGa) from the baseline period. To represent basal autonomic function, we assessed both cardiac and vascular arms of the baroreflex during the baseline period. Cardiac baroreflex sensitivity (BRSc) was estimated by applying both the “sequence” and “spectral” techniques to beat-to-beat measurements of systolic blood pressure and RRIs. The vascular baroreflex sensitivity (BRSv) was quantified using the same approaches, modified for application to beat-to-beat diastolic blood pressure and PPGa measurements. Baseline BRSc was not different between SCD and non-SCD subjects, was not correlated with BRSv, and was not associated with the vasoconstriction responses to MTS tasks. BRSv in both groups was correlated with mean PPGa, and since both baseline PPGa and BRSv were lower in SCD, these results suggested that the SCD subjects were in a basal state of higher sympathetically mediated vascular tone. In both groups, baseline BRSv was positively correlated with the vasoconstriction responses to N-back, Stroop, and PA. After adjusting for differences in BRSv within and between groups, we found no difference in the vasoconstriction responses to all three mental tasks between SCD and non-SCD subjects. The implications of these findings are significant in subjects with SCD since vasoconstriction reduces microvascular flow and prolongs capillary transit time, increasing the likelihood for vaso-occlusive crisis (VOC) to be triggered by exposure to stressful events.

The Added Value of Sensitivity to Nonnoxious Stimuli to Predict an Individual’s Sensitivity to Pain

BACKGROUND: Simple tools are needed to predict postoperative pain. Questionnaire-based tools such as the Pain Sensitivity Questionnaire (PSQ) are validated for this purpose, but prediction could be improved by incorporating other parameters. OBJECTIVES: To explore the potency of sensitivity to nonpainful stimuli and biometric data to improve prediction of pain. STUDY DESIGN: Transversal exploratory study. SETTING: Single clinical investigation center. METHODS. Eighty-five healthy volunteers of both genders underwent a multimodal exploration including biometry, questionnaire-based assessment of anxiety, depression, pain catastrophizing, sensitivity to smell, and the PSQ, followed by a psychophysical assessment of unpleasantness thresholds for light and sound, and sensitivity to mechanical, heat, and cold pain. These last 3 parameters were used to calculate a composite pain score. After a multi-step selection, multivariable analyses identified the explanative factors of experimental pain sensitivity, by including biometric, questionnaire-based, and psychophysical nonnociceptive sensitivity parameters, with the aim of having each domain represented. RESULTS: Female gender predicted mechanical pain, a younger age and dark eyes predicted cold pain, and the PSQ predicted heat pain. Sensitivity to unpleasantness of sound predicted mechanical and heat pain, and sensitivity to unpleasantness of light predicted cold pain. Sensitivity to smell was unrelated. The predictors of the composite pain score were the PSQ, the light unpleasantness threshold, and an interaction between gender and eye color, the score being lower in light-eyed men and higher in all women. The final multivariable multi-domain model was more predictive of pain than the PSQ alone (R2 = 0.301 vs 0.122, respectively). LIMITATIONS: Sensitivity to smell was only assessed by a short questionnaire and could lack relevance. Healthy volunteers were unlikely to elicit psychological risk factors such as anxiety, depression, or catastrophizing. These results have not been validated in a clinical setting (e.g., perioperative). CONCLUSION: The predictive potential of the PSQ can be improved by including information about gender, eye color, and light sensitivity. However, there is still a need for a technique suitable for routine clinical use to assess light sensitivity. KEY WORDS: Personalized medicine, postoperative pain, senses, prediction, photophobia, hyperacusis, eye color, hypervigilance, sensory over-responsivity

Delta Opioid Receptor in Astrocytes Contributes to Neuropathic Cold Pain and Analgesic Tolerance in Female Mice

Background: The delta opioid receptor (DOR) contributes to pain control, and a major challenge is the identification of DOR populations that control pain, analgesia, and tolerance. Astrocytes are known as important cells in the pathophysiology of chronic pain, and many studies report an increased prevalence of pain in women. However, the implication of astrocytic DOR in neuropathic pain and analgesia, as well as the influence of sex in this receptor activity, remains unknown.Experimental Approach: We developed a novel conditional knockout (cKO) mouse line wherein DOR is deleted in astrocytes (named GFAP-DOR-KO), and investigated neuropathic mechanical allodynia as well as analgesia and analgesic tolerance in mutant male and female mice. Neuropathic cold allodynia was also characterized in mice of both sexes lacking DOR either in astrocytes or constitutively.Results: Neuropathic mechanical allodynia was similar in GFAP-DOR-KO and floxed DOR control mice, and the DOR agonist SNC80 produced analgesia in mutant mice of both sexes. Interestingly, analgesic tolerance developed in cKO males and was abolished in cKO females. Cold neuropathic allodynia was reduced in mice with decreased DOR in astrocytes. By contrast, cold allodynia was exacerbated in full DOR KO females.Conclusions: These findings show that astrocytic DOR has a prominent role in promoting cold allodynia and analgesic tolerance in females, while overall DOR activity was protective. Altogether this suggests that endogenous- and exogenous-mediated DOR activity in astrocytes worsens neuropathic allodynia while DOR activity in other cells attenuates this form of pain. In conclusion, our results show a sex-specific implication of astrocytic DOR in neuropathic pain and analgesic tolerance. These findings open new avenues for developing tailored DOR-mediated analgesic strategies.

Factors associated with chemotherapy-induced peripheral neuropathy-related reduced taxane dose or premature discontinuation in women with early-stage breast cancer

Purpose: In the absence of treatments for chemotherapy-induced peripheral neuropathy (CIPN), dose reductions (DR) and premature discontinuation (PD) are primary management strategies. However, decision-making guidance is insufficient and knowledge of factors associated with DRPD is limited. We examined biopsychosocial factors associated with CIPN-related DR/PD in women undergoing taxane-based chemotherapy for early-stage breast cancer. Patients and methods: As part of a longitudinal study of CIPN measurement, women completed assessments before the first taxane infusion and at the final infusion or within the originally expected timeframe for the final infusion. Participants completed self-report measures of CIPN, pain, and physical and psychosocial wellbeing, and underwent physical testing of lower limb disability and Quantitative Sensory Testing for sensation and pain threshold to thermal, vibration, and touch stimuli in the feet and hands. Sociodemographic and clinical data were collected. Logistic regression was used to identify factors associated with neuropathy-related DRPD. Results: Among 121 participants, 66 (54.5%) received taxane-as-prescribed, 46 (38.0%) had neuropathy-related DRPD, and 9 (7.4%) had DR/PD for other reasons. Factors associated with neuropathy-related DR/PD were receipt of paclitaxel (Odds Ratio [OR]=75.05, 95% Confidence Interval [CI] 2.56-2197.96]), lower pre-treatment pain catastrophizing (OR=0.72, 95% CI: 0.54-0.95), and higher post-treatment neuropathic pain (OR=10.77, 95% CI: 1.99-58.15) and sensitivity to cold pain in the hand (OR=1.64, 95% CI: 1.05-2.56). Conclusion: CIPN-related DRPD is associated with paclitaxel treatment and post-treatment neuropathic pain and cold pain sensitivity in the hands. CIPN communication to healthcare providers may be influenced by pain catastrophizing, suggesting symptom appraisal may be an important factor in communication. Findings could contribute to clinical practice recommendations to facilitate treatment decision-making.

Low mechano-afferent fibers reduce thermal pain but not pain intensity in CRPS

Background Human hairy (not glabrous skin) is equipped with a subgroup of C-fibers, the C-tactile (CT) fibers. Those do not mediate pain but affective aspects of touch. CT-fiber-activation reduces experimental pain if they are intact. In this pilot study we investigated pain modulating capacities of CT-afferents in CRPS. Methods 10 CRPS-patients (mean age 33 years, SEM 3.3) and 11 healthy controls (mean age 43.2 years, SEM 3.9) participated. CT-targeted-touch (brush stroking, velocity: 3 cm/s) was applied on hairy and glabrous skin on the affected and contralateral limb. Patients rated pleasantness of CT-targeted-touch (anchors: 1 “not pleasant”—4 “very pleasant”) twice daily on 10 days. Pain intensity (NRS: 0 “no pain” – 10 “worst pain imaginable”) was assessed before, 0, 30, 60 and 120 min after each CT-stimulation. To assess sensory changes, quantitative-sensory-testing was performed at the beginning and the end of the trial period. Results CT-targeted-touch was felt more pleasant on the healthy compared to the affected limb on hairy (p < 0.001) and glabrous skin (p 0.002), independent of allodynia. In contrast to healthy controls patients felt no difference between stimulating glabrous and hairy skin on the affected limb. Thermal pain thresholds increased after CT-stimulation on the affected limb (cold-pain-threshold: p 0.016; heat-pain-threshold: p 0.033). Conclusions CT-stimulation normalizes thermal pain thresholds but has no effect on the overall pain in CRPS. Therefore, pain modulating properties of CT-fibers might be too weak to alter chronic pain in CRPS. Moreover, CT-fibers appear to lose their ability to mediate pleasant aspects of touch in CRPS.

Pain and the Emotional Brain: Affective Rather than Cognitive Processes Drive the Cortical Encoding of Pain

The experience of pain has been dissociated into two interwoven aspects: a sensory-discriminative aspect assessed in ratings of pain intensity and an affective-motivational aspect assessed in ratings of unpleasantness. In a pain attenuation paradigm, participants were asked to evaluate applied cold pain. The majority of the trials showed a distinct rating: Some trials were rated higher for unpleasantness, others were rated higher for intensity. Using linear mixed effect models on single trials, we related the variable difference between unpleasantness and intensity ratings to functional MRI data. The direct comparison revealed a stronger relationship between cortical data and pain ratings for unpleasantness. No region showed a stronger effect for pain intensity. The present study underlines the importance of the emotional-affective aspects of pain-related cortical processes in the brain. These findings reflect the biological function of the pain system to prevent harm and to preserve the physical integrity of the body.