Displaying publications 21 - 40 of 2661 in total

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  1. Stanton AT, Fletcher W
    Matched MeSH terms: Rats
  2. Nor Malia Abd Warif, Asyraf Akmal Ayob, Wan Marahaini Wan Razali, Siti Balkis Budin, Satirah Zainalabidin, Jamaludin Mohamed
    MyJurnal
    Disturbances in immune system contribute to chronic infection among diabetic patients. Hibiscus sabdariffa L. (roselle) fruit extract has been scientifically proven to possess antioxidant, antidiabetic and antiinflammatory properties. The aim of this study was to investigate the effects of H. sabdariffa fruit extract against oxidative stress parameter and T lymphocyte population in spleen of streptozotocin (STZ) induced diabetic rats. Male Sprague-Dawley rats were injected with 45 mg/kg STZ to induce diabetic condition and further treated with 100 mg/kg H. sabdariffa fruit aquoeus extract daily for 28 days. Spleen was harvested to determine the oxidative stress indicators and quantification of T lymphocytes. The results showed a significant decreased in the number of spleen cells and spleen weight in the diabetic rats compared with control rats. However, there were no significant changes in the level of malondialdehyde (MDA), protein carbonyl and superoxide dismutase (SOD) activity the percentage of spleen CD3+ CD4+ and CD3+ CD8+ T lymphocytes amongst groups of study. In addition, histology observation showed no pathological alteration in spleen histology of diabetic rats. The findings suggested that aqueous extract of H. Sabdariffa fruit supplementation has no effect on the oxidative stress and the percentage of CD3+ CD4+ and CD3+ CD8+ T lymphocytes in spleen of diabetic rats.
    Keywords: Diabetes, H. sabdariffa, spleen, oxidative stress, T lymphocytes
    Matched MeSH terms: Rats
  3. Fletcher W, Lesslar JE, Lewthwaite R
    Trans R Soc Trop Med Hyg, 1928;22:161-162.
    DOI: 10.1016/S0035-9203(28)90008-5
    A short description of the tsutsugamushi disease is given, followed by a note on the conditions under which it occurs in Sumatra and the Malay States. Abandoned agricultural land which has grown up in weeds is particularly dangerous. Small rodents are the reservoirs of the virus which is carried from them to man by larval mites. Trombicula akamushi is the carrier in Japan, and T. deliensis in Sumatra. The disease has been conveyed to monkeys by inoculation and also by the bites of infected mites. A description is given of four mites which are commonly found in the ears of rats in the Malay States, and a method for the examination of the mites is described. Black rats, to the number of 130, were examined. Sixteen were trapped in an abandoned portion of an oil-palm estate where three Europeans became infected with the tsutsugamushi disease, and T. deliensis, the Sumatran carrier, was found on ten of them. Thirty rats were caught in other parts of the estate, and T. deliensis was found on nine. Thirty rats were caught in other rural districts, where the disease was not known, and T. deliensis was found on only one. Fifty-four rats caught in the town of Kuala Lumpur were examined, with the result that T. deliensis was found in none. The conclusion is reached that T. deliensis is probably the carrier in the Malay States, as it is in Sumatra.
    Matched MeSH terms: Rats
  4. Lewthwaite R, Savoor SR
    Br J Exp Pathol, 1936;17:208.
    (1) Two strains of tropical typhus have been isolated from wild rats trapped in endemic areas.
    (2) Both were isolated and maintained in guinea-pigs.
    (3) One could be isolated in rabbits by the intra-ocular inoculation of virus, and maintained thus indefinitely. The features of this infection appeared to be identical with corresponding infections obtained with the viruses of rural typhus and the tsutsugamushi disease of human origin. Repeated attempts to isolate the other rat strain in rabbits in the same manner failed.
    (4) Rickettsia were found with ease and in abundance in infected material from guinea-pigs infected with either strain, and from rabbits infected with the one-strain.
    (5) The sera of rabbits infected with the two rat strains gave positive Weil-Felix reactions of significant titre.
    (6) Cross-immunity tests in rabbits between one rat strain and six strains of huinan origin of rural typhus and tsutsugamushi showed a cross-immunity to exist, complete in five strains and partial in the sixth strain.
    (7) A concomitant infection with sodoku was present in the guinea-pigs of botlh strains ; although this may have modified the clinical signs, the infection by a typhus virus could be determined by four decisive criteria.
    (8) The conclusion is drawn that the murine origin of the virus of the rural typhus-tsutsugamuslhi group of diseases is now firmly established.
    Matched MeSH terms: Rats
  5. Malaya Medical Journal, 1912;10:9-26.
    Matched MeSH terms: Rats
  6. Abdulabbas Hasan M, Mohan S, Rahman HS, Othman HH, Hamasalih Omer S, Farasani A
    Drug Chem Toxicol, 2023 May;46(3):588-596.
    PMID: 35506235 DOI: 10.1080/01480545.2022.2069803
    Kava is a herbal supplement and beverage made from the Piper methysticum plant, which is known for its recreational use as a mood enhancer, relaxation, as well as pain relief for centuries. Kava is widely used among alcoholics, but it is dangerous and potentially fatal. The objectives of this study were to examine the sub-acute toxicity effects of different doses of 70% kavalactone (KL) in rats by oral application, as well as to elucidate the mechanisms of toxicity alone and in combination with ethanol (EtOH). The most common side effects observed were abnormal breathing, ataxia, lethargy, loss of appetite, indigestion, and loss of coordination, especially in the 800 mg/kg bw, po bodyweight dosage of kava treatment group alone, and in combination with EtOH. In the sub-acute study, there were dose-related decreases in body weight, feed intake, and water consumption rates. Gross and histopathological findings revealed that the liver was abnormal in color, size, consistency, and the weight significantly increased at a dose of 800 mg/kg bw, po, with KL alone and a greater increase in combination with EtOH. Hepatocellular hypertrophy (HP) and necrosis with Kupffer cells hyperplasia were observed in the periacinar zone of all rats dosed with KL (800 mg/kg bw, po) alone, and extensive changes were observed in combination with EtOH. The periportal (Z1) and mid-zonal (Z2) areas of hepatocytes were less affected as compared to the periacinar zone. These results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity. The histopathological results supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner.
    Matched MeSH terms: Rats
  7. Al Bayaty FH, Mahmod SA, Jamil Al-Obaidi MM, Emad Ibrahim O, Dahir A, Adam FA, et al.
    J Periodontal Res, 2023 Feb;58(1):22-28.
    PMID: 36321414 DOI: 10.1111/jre.13064
    BACKGROUND: There is scarce information about the relationship between periodontal disease and osteoarthritis. This study investigated the effect of surgically induced osteoarthritis on alveolar bone loss in experimental periodontitis in rats.

    METHODS: 12 rats were divided into test and control groups. On day 1, the animals were anaesthetized, and silk ligatures were ligated around 6 maxillary posterior teeth in each animal from both groups. Surgical induction of osteoarthritis was performed on the left knees in the test group. No knee surgeries were performed in the control group. The ligatures were kept in place for 30 days, at which time the animals were euthanatized, and the maxillae and knee joints were harvested and processed for histological analysis. The alveolar bone loss was assessed using a zoom stereomicroscope.

    RESULTS: The knee joint histologic sections of the control group showed normal joint features, whereas in the test group there were substantial changes typical of osteoarthritis, including wide joint spaces, prominent monocytic infiltration of the synovium, invasion of periarticular bone, and decreased chondrocyte density. Comparison of the bone height between the groups showed a significantly higher bone loss in the test than in the control group The marginal mean bone height, adjusted for covariates and the intraclass correlation between sites, was 1.19 and 0.78 mm in the test and control groups, respectively (p 

    Matched MeSH terms: Rats
  8. Ibrahim MY, Hashim NM, Omer FAA, Abubakar MS, Mohammed HA, Salama SM, et al.
    Int J Mol Sci, 2023 Jun 17;24(12).
    PMID: 37373429 DOI: 10.3390/ijms241210283
    In this study, the chemotherapeutic effect of α-mangostin (AM) was assessed in rats injected with LA7 cells. Rats received AM orally at 30 and 60 mg/kg twice a week for 4 weeks. Cancer biomarkers such as CEA and CA 15-3 were significantly lower in AM-treated rats. Histopathological evaluations showed that AM protects the rat mammary gland from the carcinogenic effects of LA7 cells. Interestingly, AM decreased lipid peroxidation and increased antioxidant enzymes when compared to the control. Immunohistochemistry results of the untreated rats showed abundant PCNA and fewer p53-positive cells than AM-treated rats. Using the TUNEL test, AM-treated animals had higher apoptotic cell numbers than those untreated. This report revealed that that AM lessened oxidative stress, suppressed proliferation, and minimized LA7-induced mammary carcinogenesis. Therefore, the current study suggests that AM has significant potential for breast cancer treatment.
    Matched MeSH terms: Rats
  9. Abdul-Majeed S, Mohamed N, Soelaiman IN
    PMID: 22927884 DOI: 10.1155/2012/960742
    Statins are HMGCoA reductase inhibitors and had been demonstrated to stimulate bone formation in rodents after high oral doses. Observational studies on patients treated with oral statins were varied. Delta-tocotrienol had been found to stimulate the cleavage of HMGCoA reductase and inhibit its activity. Tocotrienols were found to have both catabolic and anabolic effects on bone in different animal models of osteoporosis. The current study aimed to ascertain the effects of delta-tocotrienol and lovastatin combination on biochemical and static bone histomorphometric parameters in a postmenopausal rat model at clinically tolerable doses. 48 Sprague Dawley female rats were randomly divided into 6 groups: (1) baseline control group; (2) sham-operated control group; (3) ovariectomised control group; (4) ovariectomised and 11 mg/kg lovastatin; (5) ovariectomised and 60 mg/kg delta-tocotrienol; (6) ovariectomised and 60 mg/kg delta-tocotrienol + 11 mg/kg lovastatin. These treatments were given daily via oral gavage for 8 weeks. Delta-tocotrienol plus lovastatin treatment significantly increased bone formation and reduced bone resorption compared to the other groups. Therefore, the combined treatment may have synergistic or additive effects and have the potential to be used as an antiosteoporotic agent in patients who are at risk of both osteoporosis and hypercholesterolemia, especially in postmenopausal women.
    Matched MeSH terms: Rats, Sprague-Dawley
  10. Fathilah SN, Abdullah S, Mohamed N, Shuid AN
    PMID: 22991574
    Estrogen replacement therapy (ERT) is the main treatment postmenopausal osteoporosis. However, ERT causes serious side effects, such as cancers and thromboembolic problems. Labisia pumila var. alata (LPva) is a herb with potential as an alternative to ERT to prevent complications of osteoporosis, especially fragility fractures. This study was conducted to determine the effects of LPva on the biomechanical strength of femora exposed to osteoporosis due to estrogen deficiency, using the postmenopausal rat model. Thirty-two female rats were randomly divided into four groups: Sham-operated (Sham), ovariectomized control (OVXC), ovariectomized with Labisia pumila var. alata (LP), and ovariectomized with ERT (Premarin) (ERT). The LPva and ERT were administered via oral gavage daily at doses of 17.5 mg/kg and 64.5 μg/kg, respectively. Following two months of treatment, the rats were euthanized, and their right femora were prepared for bone biomechanical testing. The results showed that ovariectomy compromised the femoral strength, while LPva supplementation to the ovariectomized rats improved the femoral strength. Therefore, LPva may be as effective as ERT in preventing fractures due to estrogen-deficient osteoporosis.
    Matched MeSH terms: Rats
  11. Ilmie MU, Mansor SM, Abdullah JM
    Malays J Med Sci, 2015 Dec;22(Spec Issue):45-51.
    PMID: 27006637 MyJurnal
    BACKGROUND: Mitragyna speciosa (MS) or ketum is primarily found in Southeast Asia, particularly in northern Malaysia and Thailand. The medicinal value of this plant has attracted significant attention from both herbal medicine practitioners and scientists worldwide. Despite having illegal consumption status, the plant merits study. We conducted a series of experiments to test our hypothesis that ketum impairs both learning and memory in rats.
    METHODS: Ketum leaves were extracted using methanol and standardised for the amount of its pure compound, mitragynine. Rats were divided into groups for a passive avoidance task and long-term potentiation (LTP) extracellular recording. In the extracellular recording condition, rats were grouped into control, MS100 (100 mg/kg of ketum extract), MS200 (200 mg/kg of ketum extract), and MS500 (500 mg/kg of ketum extract) groups. An additional group that received morphine was included in the passive avoidance task (10 mg/kg), and there were six animals per group. Rats received daily treatments orally for 28 days for both experiments.
    RESULT: Using a passive avoidance task, our data revealed that the rats' memory significantly increased with increasing doses of MS compared to the morphine-treated group. Our findings from LTP recordings showed that LTP was fully blocked by the higher doses of MS.
    CONCLUSION: We speculate on the possibility that additional factors were involved in the passive avoidance task because it was an in vivo animal study, while the LTP experiment solely involved brain slices.
    Matched MeSH terms: Rats, Sprague-Dawley
  12. Kan SP, Dissanaike AS
    Z Parasitenkd, 1977 Jul 29;52(3):219-27.
    PMID: 410181
    The ultrastructure of Sarcocystis sp. from the Malaysian house rat, Rattus rattus diardii, was studied with the electron microscope. The thin, uniformly-dense primary cyst wall had a row of vesicular invaginations which were also seen along the wall of the villi-like projections or cytophaneres. Within the villi were spherical bodies and hollow, curled structures. The ground substance beneath the primary cyst wall extended into the cyst as thin septa or trabeculae separating the tightly-packed zoites into compartments. Merozoites had a double-layered membrane, a conoid, 2 conoidal rings, 22 subpellicular microtubules, 6 rhoptries, 80-100 micronemes, scattered lipid droplets, and sac-like mitochrondrion, beside which was a Golgi apparatus. A micropore was occasionally seen at the anterior third of the zoite whereas the nucleus occupied the posterior third. Metrocytes were few in number and peripheral in location.
    Matched MeSH terms: Rats/parasitology
  13. Salem SA, Rashidbenam Z, Jasman MH, Ho CCK, Sagap I, Singh R, et al.
    Tissue Eng Regen Med, 2020 08;17(4):553-563.
    PMID: 32583275 DOI: 10.1007/s13770-020-00271-7
    BACKGROUND: The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such as cancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventual reconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one major problem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them. Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladder reconstruction.

    METHODS: Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells and then seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinary bladder resection and were divided into three treatment groups (n = 3): Group 1 ("sham") underwent anastomosis of the remaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstruction with the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation was performed whenever a decline in animal health was detected.

    RESULTS: All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weeks post-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred in Group 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that the urinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiological evaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysis revealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemical staining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of the seeded cells in the newly regenerated muscular layers.

    CONCLUSION: Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stem cells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completely functional urinary bladder.

    Matched MeSH terms: Rats, Nude; Rats
  14. Betterton C, Lim BL
    PMID: 816008
    Neodiplostomum (Conodiplostomum) Brachylaima, Ectosiphonus and Euparadistomum are reported for the first time from small mammals in Malaysia. New host and locality records are given for Echinostoma, Achillurbainia, Beaveria, Odeningotrema, Leipertrema, Athesmia, Skrjabinus and Zonorchis. Possible-life-cycles of the parasites are discussed in relation to the ecology and feeding habits of the hosts.
    Matched MeSH terms: Rats/parasitology*
  15. W.I. Wan Rosli, M.A. Solihah, A.R. Nurhanan, W.A. Wan Amir Nizam
    Sains Malaysiana, 2015;44:1167-1174.
    Cornsilk is traditionally used to treat illnesses related to kidney and as diuretic agent. The study was performed to evaluate the effectiveness of Malaysian cornsilk in elevating diuresis and their dose response relationship in normal Sprague-Dawley rat. The diuresis activity was determined by administered the rats with different dose treatments of 400, 500, 600, 700 and 800 mg/kg. Cumulative urine was significantly increased with the dosage levels (400-600 mg/ kg) ranging from 14.06 - 20.13 mL. Cumulative urine of aqueous extract of cornsilk (AEC) at 400 mg/kg (14.06 mL) and 500 mg/kg (15.21 mL) treatments found to be significantly lower than positive control (21.25 mL). In addition, Na+ content was significantly higher compared with negative control at dosages of 500, 600, 700 and 800 mg/kg. At any rate, K+ and Cl- content of all AEC treatments were not significantly different during 24 h monitoring. The pH values were increased paralleled with the increment of AEC dosages, though it was not significant. On the other result, the ED50 of AEC was observed at 454.10 mg/kg. Malaysian AEC had shown a mild diuretic activity in elevating urine and Na+ content at dosages from 500 to 800 mg/kg. Whilst, AEC also showed an effect of potassium sparing diuretics. Thus, it is suggested that Malaysian cornsilk can be used as an alternative natural diuretic agent.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  16. Kaur A, Dhiman S, Lee HB, Sharma M
    Anticancer Agents Med Chem, 2022;22(18):3182-3192.
    PMID: 35469577 DOI: 10.2174/1871520622666220425114553
    BACKGROUND: Camptothecin is a naturally occurring alkaloid obtained from the stem wood of the Chinese tree, Camptotheca acuminata. It exerts pharmacological effects due to its ability to selectively inhibit the type-I topoisomerase DNA nuclear enzyme. Several semisynthetic analogs of camptothecin have been synthesized to date possessing antitumor activity.

    OBJECTIVE: Camptothecin (CPT) is one of the most promising anticancer drugs but it produces various side effects because of its non-selectivity towards cancer cells. To overcome these adverse effects, we synthesized biotin conjugate of camptothecin, which was linked via a self-immolative disulfide linker (CPT-SS-Biotin).

    METHODS: Biotin conjugated camptothecin linked through a disulfide bond was synthesized following schemes, and the structural characterization was carried out. The stability and drug release studies were performed in the presence of glutathione (GSH) while in vitro studies were performed on 4T1 tumor cell lines. In vivo pharmacological investigation was done using an antitumor Wistar rat model.

    RESULTS: The stability and drug release studies were performed in the presence of glutathione (GSH), and CPT-SSBiotin was found to be physiologically stable moiety and can only be cleaved in the presence of GSH to release free CPT. The CPT-SS-Biotin showed higher toxicity in the biotin-overexpressing 4T1 tumor cell line with a lower IC50 value (8.44 μM) compared to camptothecin alone (IC50 > 30 μM). CPT-SS-Biotin also showed 10.6% higher cellular uptake by cells in comparison to free camptothecin. The CPT-SS-Biotin was delivered to cells by binding to the biotin receptors on the cell surface, followed by energy-dependent endocytosis and internalization to cause cellular toxicity.

    CONCLUSION: In-vivo tumor suppression studies and in vitro cell line studies along with serological parameters and histopathological studies showed that conjugate produced a high therapeutic effect and remarkably reduced toxic effects in comparison to free CPT. The results suggested that biotinylation of camptothecin via disulfide linker can be a safe and efficacious method in cancer therapeutics.

    Matched MeSH terms: Rats, Wistar; Rats
  17. Akansha EO, Bui BV, Ganeshrao SB, Bakthavatchalam P, Gopalakrishnan S, Mattam S, et al.
    Int J Environ Res Public Health, 2022 Oct 09;19(19).
    PMID: 36232222 DOI: 10.3390/ijerph191912922
    Evidence suggests that prolonged blue-light exposure can impact vision; however, less is known about its impact on non-visual higher-order functions in the brain, such as learning and memory. Blue-light-blocking lenses (BBLs) claim to reduce these potential impacts. Hence, we assessed structural and functional hippocampal alterations following blue-light exposure and the protective efficacy of BBLs. Male Wistar rats were divided into (n = 6 in each group) normal control (NC), blue-light exposure (LE), and blue-light with BBLs (Crizal Prevencia, CP and DuraVision Blue, DB) groups. After 28 days of light exposure (12:12 light: dark cycle), rats were trained for the Morris water maze memory retention test, and brain tissues were sectioned for hippocampal neuronal analysis using Golgi and Cresyl violet stains. The memory retention test was significantly delayed (p < 0.05) in LE compared with DB groups on day 1 of training. Comparison of Golgi-stained neurons showed significant structural alterations, particularly in the basal dendrites of hippocampal neurons in the LE group, with BBLs significantly mitigating these structural changes (p < 0.05). Comparison of Cresyl-violet-stained neurons revealed significantly (p < 0.001) increased degenerated hippocampal neurons in LE rats, with fewer degenerated neurons in the CP lens group for CA1 neurons (p < 0.05), and for both CP and DB groups (p < 0.05) for CA3 neurons. Thus, in addition to documented effects on visual centers, high-level blue-light exposure also results in degeneration in hippocampal neurons with associated behavioral deficits. These changes can be partially ameliorated with blue-light-blocking lenses.
    Matched MeSH terms: Rats, Wistar; Rats
  18. Pramana IGAN, Hariani L, Zarasade L
    Med J Malaysia, 2023 Jul;78(4):484-487.
    PMID: 37518916
    INTRODUCTION: Effective antiseptic use is essential in healthcare settings to prevent the spread of diseases, especially in areas with high patient traffic and exposure to various pathogens. One essential pathogenic germ is Acinetobacter baumannii. Octenidine and povidone-iodine have been demonstrated to be effective against A. baumannii in vitro. This study will compare octenidine dihydrochloride and povidone-iodine as wound-cleansing solutions for wounds contaminated with A. baumannii in vivo.

    MATERIALS AND METHODS: Twenty-four rats were divided into three groups: normal saline, octenidine dihydrochloride and povidone-iodine. Wounds were made on the rats' backs, and A. baumannii germs were inoculated into the wounds. After 3 hours, the wound was irrigated with wound cleansing solution according to the group for 30 seconds. Each wound was taken swab culture before and after wound irrigation and tissue culture 5 hours after wound irrigation.

    RESULTS: All specimens showed bacterial colony growth with a median value of 1.22 × 105 CFU before irrigation. Wound irrigation with normal saline did not reduce colony counts, while there was a 3-log reduction to 5-log reduction in the octenidine and povidone-iodine groups. Statistically, there was no significant difference in the mean number of colonies between the octenidine and povidone-iodine groups after irrigation (p = 0.535). However, 3 hours after irrigation, all specimens that experienced 3-log reduction showed regrowth to more than 1 × 105 CFU. In contrast, specimens subjected to 5-log reduction did not exhibit any regrowth.

    CONCLUSION: The antiseptic effectiveness of octenidine dihydrochloride is equivalent to povidone-iodine in eradicating A. baumannii colonies in wounds in vivo.

    Matched MeSH terms: Rats, Wistar; Rats
  19. Lee MT, Peng WH, Wu CC, Kan HW, Wang DW, Teng YN, et al.
    Mol Neurobiol, 2023 Oct;60(10):5708-5724.
    PMID: 37338803 DOI: 10.1007/s12035-023-03439-z
    Chronic pain conditions within clinical populations are correlated with a high incidence of depression, and researchers have reported their high rate of comorbidity. Clinically, chronic pain worsens the prevalence of depression, and depression increases the risk of chronic pain. Individuals suffering from chronic pain and depression respond poorly to available medications, and the mechanisms underlying the comorbidity of chronic pain and depression remain unknown. We used spinal nerve ligation (SNL) in a mouse model to induce comorbid pain and depression. We combined behavioral tests, electrophysiological recordings, pharmacological manipulation, and chemogenetic approaches to investigate the neurocircuitry mechanisms of comorbid pain and depression. SNL elicited tactile hypersensitivity and depression-like behavior, accompanied by increased and decreased glutamatergic transmission in dorsal horn neurons and midbrain ventrolateral periaqueductal gray (vlPAG) neurons, respectively. Intrathecal injection of lidocaine, a sodium channel blocker, and gabapentin ameliorated SNL-induced tactile hypersensitivity and neuroplastic changes in the dorsal horn but not depression-like behavior and neuroplastic alterations in the vlPAG. Pharmacological lesion of vlPAG glutamatergic neurons induced tactile hypersensitivity and depression-like behavior. Chemogenetic activation of the vlPAG-rostral ventromedial medulla (RVM) pathway ameliorated SNL-induced tactile hypersensitivity but not SNL-elicited depression-like behavior. However, chemogenetic activation of the vlPAG-ventral tegmental area (VTA) pathway alleviated SNL-produced depression-like behavior but not SNL-induced tactile hypersensitivity. Our study demonstrated that the underlying mechanisms of comorbidity in which the vlPAG acts as a gating hub for transferring pain to depression. Tactile hypersensitivity could be attributed to dysfunction of the vlPAG-RVM pathway, while impairment of the vlPAG-VTA pathway contributed to depression-like behavior.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
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