AIMTo observe the changes of nitric oxide synthase (NOS) activity and nitric oxide (NO) content of hippocampus including their time course and region distribution character in rat during the process of formalin-induced inflammatory pain as well as the pain behavior of rat.

METHODSThe pain threshold (PT) was determined by radiant heat-induced tail flick test. NOS expression in the hippocampus was determined by using NADPH-d histochemical staining. NO production in hippocampus was determined by assaying NO3- and NO2-.

RESULTSSubcutaneous injection of formalin elicited nociceptive behavioural response and led to decrease in PT of rat. The number and staining degree of NADPH-d positive neurons began to increase at 6 h after the formalin injection in CA1, CA2 - 3 and DG of hippocampus as well as NO content, which increased most obviously at 12 h and returned to control level at 48 h.

CONCLUSIONFormalin-induced inflammatory pain could induce the elevation of NOS activity in CA1, CA2 - 3 and DG of hippocampus with a certain time course, which further led to a increase of NO production in hippocampus.

Animals ; Formaldehyde ; adverse effects ; Hippocampus ; metabolism ; Inflammation ; chemically induced ; metabolism ; Male ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase ; metabolism ; Pain ; chemically induced ; metabolism ; Pain Threshold ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the changes in the levels of monocarboxylate transporter-2 in spinal cord horn in a rat model of chronic inflammatory pain.

METHODSMale SD rats weighting 180 - 220 g were randomly divided into two groups(n = 48): normal saline group (NS group), complete Freund's adjuvant group (CFA group). Rats were given injections of CFA 100 µl in left hind paw in group CFA, and an equal volume of saline was given injection in group NS. Mechanical withdraw threshold(MWT) and thermal withdraw latency(TWL) were measured at before injection(T0 and 3 h, 1 d, 3 d, 7 d, 14 d, and 21 d after injection(T1-7). Four rats were chosen from each group at T0-7 and sacrificed, and L4-5 segments of the spinal cord horn were removed for measurement of the expression of monocarboxylate transporter-2 by Western blot analysis.

RESULTSIn CFA group, mechanical hyperalgesia and allodynia appeared on the 3 h after CFA injection, then until the day 14. The expression of monocarboxylate transporter-2 in the spinal dorsal horn of rats in CFA group was significantly higher than that in normal control group at T1-6(P <0.05). The protein level of monocarboxylate transporter-2 was apparently correlated with MWT and TWL(P <0.01 and P <0.05) in CFA group.

CONCLUSIONThe level of monocarboxylate transporter-2 in spinal dorsal horn is significantly increased in a rat model of chronic inflammatory pain and the change may involve in the formation and maintenance of central sensitization in spinal cord of chronic inflammatory uain.

Animals ; Disease Models, Animal ; Freund's Adjuvant ; Hyperalgesia ; chemically induced ; Inflammation ; chemically induced ; metabolism ; Male ; Monocarboxylic Acid Transporters ; metabolism ; Pain ; chemically induced ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; metabolism ; physiopathology

OBJECTIVETo analyze the clinical features and diagnostic points of occupational acute dimethylformamide (DMF) poisoning and to explore the mechanism of occupational acute DMF poisoning.

METHODSA comprehensive analysis was performed on the clinical data of 16 cases of occupational acute DMF poisoning, including symptoms, signs, and laboratory testing results.

RESULTSThe main clinical features of occupational acute DMF poisoning were digestive system impairments, especially abdominalgia. Hemorrhagic gastroenteritis was not found by gastroscopy. There was no significant correlation between the degree of abdominalgia and alanine aminotransferase level (r(s) = 0.109, P>0.05).

CONCLUSIONAbdominalgia is recommended to be one of the reference indices for the diagnosis and degrading of occupational acute DMF poisoning, The mechanism of DMF poisoning remains unclear but it is considered to be related to methyl isocyanate, the intermediate product of DMF metabolism.

Abdominal Pain ; chemically induced ; Alanine Transaminase ; metabolism ; Dimethylformamide ; poisoning ; Humans ; Occupational Exposure ; Solvents ; poisoning

AIMTo investigate whether formalin inflammatory pain can induce hippocampal neuronal apoptosis of rats or not.

METHODSRats were subcutaneously injected with 0.2 ml 0.5% formalin into the ventral surface of right hind paw to induce periphery inflammatory pain. The flinches of rats were counted to observe their painful reaction. Flow cytometry was used to assay the ratio of apoptosis of hippocampal neurons. The immunohistochemistry was used to observe the expression of p53 protein in hippocampal subregions.

RESULTSCompared with control group, the apoptotic ratio of hippocampal neurons was significantly increased in rats with inflammatory pain, and formalin inflammatory pain induced upregulation of p53 protein expression in all hippocampal subregions. Both the apoptotic ratio and the p53 protein expression peaked on the third day after the formalin injection. The twice injection of formalin into the hind paws of rats resulted in an enhancement of painful reaction and increase in apoptotic ratio of hippocampal neurons compared with the rats of injection formalin once group.

CONCLUSIONFormalin inflammatory pain can induce the hippocampal neuronal apoptosis in rats with a certain time course. Neuronal apoptosis is relevant to the intensity of pain. The up-regulation of p53 protein expression may implicate in the induction of hippocampal neuronal apoptosis in rats with inflammatory pain.

Animals ; Apoptosis ; Formaldehyde ; Hippocampus ; pathology ; physiopathology ; Inflammation ; chemically induced ; physiopathology ; Male ; Neurons ; pathology ; Pain ; chemically induced ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Suppressor Protein p53 ; metabolism

Animals ; Brain ; cytology ; Cerebrospinal Fluid ; physiology ; Formaldehyde ; administration & dosage ; toxicity ; Inflammation ; chemically induced ; physiopathology ; Male ; Neurons ; metabolism ; physiology ; Pain ; chemically induced ; physiopathology ; Pain Measurement ; methods ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; metabolism

By means of Fos immunocytochemistry, nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and microinjection methods, the role of nitric oxide synthase (NOS) of dorsal raphe (DR) neurons in the modulation of rats sigmoid pain was studied. The results showed: (1) Rats exhibited aversive behavioral responses related to visceral pain after injecting formalin into the sigmoid wall. NOS neurons in DR were up-regulated, in addition, about 8% of NOS-labeled neurons were Fos positive. By contrast, there were no Fos/NOS double-labeled neurons in the control group. (2) Formalin-induced sigmoid pain scores and the expression of Fos in the spinal cord at S1 segment were decreased after microinjecting L-NAME into the DR. These findings suggest that NOS neurons are involved in the modulation of formalin-induced sigmoid pain and that NO may play an important role in the transmission of visceral nociceptive message in the midbrain.
Analgesics ; pharmacology ; Animals ; Genes, fos ; Microinjections ; NG-Nitroarginine Methyl Ester ; pharmacology ; Neurons ; physiology ; Nitric Oxide Synthase ; metabolism ; Nociceptors ; physiology ; Pain ; chemically induced ; physiopathology ; Pain Measurement ; Raphe Nuclei ; physiology ; Rats ; Rats, Sprague-Dawley ; Sigmoid Diseases ; chemically induced ; physiopathology

AIMCCK is one of the strongest endogenous anti-opioid substances and suppresses morphine tolerance which results from long term use of morphine. This study explores the modulatory effect of CCK on pain formalin-induced.

METHODSThe effect of formalin-induced pain on CCK immunoreactivity in rat sensory neurons was observed through immunohistochemistry technique.

RESULTSAfter 1 h of subcutaneous injection of formalin in one paw of rats, the number of positive neurons of CCK immunoreactivity in spinal cord neurons was obviously increased and greater than that of non-injection side (P <0.01). The semi-quantitative optical density average values of CCK immunoreactivity neurons were 0.397 +/- 0.014 and 0.295 +/- 0.007 in injection side and non-injection side respectively, the difference was obvious (P < 0.01). After 3 h of subcutaneous injection of formalin in one paw of rats, the semi-quantitative optical density average values of CCK immunoreactivity neurons were 0.366 +/- 0.009 and 0.303 +/- 0.005 in injection side and noninjection side respectively, the difference was significant (P < 0.01).

CONCLUSIONFormalin-induced pain can significantly change semi-quantitative optical density average value of CCK immunoractivity in spinal cord neurons, this indicates CCK participates in modulation of pain.

Animals ; Cholecystokinin ; metabolism ; physiology ; Female ; Formaldehyde ; Male ; Neurons ; metabolism ; Pain ; chemically induced ; physiopathology ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Cholecystokinin ; metabolism ; physiology ; Spinal Cord ; metabolism ; pathology

AIMTo observe the changes of cyclooxygenase-2 (COX-2) expression and especially the time course of the changes in dorsal horn of the spinal cord during formalin-induced inflammatory pain and hyperalgesia in rats.

METHODSCOX-2 immunohistochemistry staining was used in rat formalin pain model.

RESULTSCompared with control group the number and immunostaining density of COX-2 immunoreactive cells in the laminae I-VI of the dorsal horn of the spinal cord increased significantly 4 h, 1 d and 3 d after formalin injection (P < 0.05). The most obvious increase was observed 1 d after the injection.

CONCLUSIONCOX-2 in the dorsal horn of the spinal cord is involved in the formalin-induced inflammatory pain and hyperalgesia.

Animals ; Cyclooxygenase 2 ; metabolism ; Formaldehyde ; adverse effects ; Pain ; chemically induced ; metabolism ; Posterior Horn Cells ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; metabolism

OBJECTIVE: To determine the changes of Mu-opioid receptor (Mor) and neuron-restrictive silencer factor (NRSF) in periaquductal gray (PAG) in mouse models of remifentanil-induced postoperative hyperalgesia. METHODS: Thirty-two Kun-Ming mice were randomly divided into 4 groups (8 mice in each group): Group C (mice underwent a sham procedure and saline was infused subcutaneously over a period of 30 min), Group I (mice underwent a surgical incision and the same volume of saline), Group R (mice underwent a sham procedure and remifentanil was infused subcutaneously at the moment of surgical incision over a period of 30 min), and group IR (mice underwent a surgical incision and remifentanil). Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) tests were performed 24 h before the operation and 2, 6, 24, and 48 h after the operation. The specimens were collected after behavioral testings at 48 h. The expressions of Mor and NRSF in mice's PAG neurons were determined by Western blot. RESULTS: Mechanical allodynia and thermal hyperalgesia developed in Group I, R and IR (P<0.01). Intraoperative infusion of remifentanil enhanced mechanical allodynia and thermal hyperalgesia in mice with planta incision (P<0.01). In Group R and Group IR, the expression of Mor was significantly lower (P<0.01) and NRSF was significantly higher (P<0.01) when compared with Group C and Group I. CONCLUSION Intraoperative infusion of remifentanil induces postoperative hyperalgesia in mouse models, accompanied with decreased expressions of Mor and increased of NRSF level in PAG neurons, which may be involved in remifentanil induced hyperalgesia.
Animals ; Disease Models, Animal ; Hyperalgesia ; chemically induced ; Mice ; Pain, Postoperative ; Periaqueductal Gray ; drug effects ; metabolism ; Piperidines ; administration & dosage ; Receptors, Opioid, mu ; metabolism ; Remifentanil ; Repressor Proteins ; metabolism

OBJECTIVETo observe the effect of electroacupuncture (EA) on phosphorylation of spinal NR2B at Tyr 1742 site in complete Freund's adjuvant (CFA) induced inflammatory pain rats. METHods Forty male Sprague Dawley rats were randomly divided into normal group (N group, n = 10), the model group (CFA group, n = 15), and the EA group (n = 15). The inflammatory pain model was established by subcutaneous injecting CFA (0.1 mL per rat) into the right hind paw. Paw withdrawal thresholds (PWTs) were measured before CFA injection (as the base), as well as at 24 h, 25 h, 3rd day, and 7th day after CFA injection. Phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn at the 3rd day post-injection were detected using immunohistochemical assay.

RESULTSPWTs in the CFA group were significantly lower than those of the N group at every detective time point post-injection (P < 0.01). PWTs were obviously lower in the EA group than in the N group at 24 h post-injection (P < 0.01). It showed increasing tendency, markedly higher than those of the CFA group at 25 h and 3rd day post-injection (P < 0.01). Compared with the N group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats in the CFA group was up-regulated. Compared with the CFA group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats showed a decreasing tendency in the EA group.

CONCLUSIONEA might effectively inhibit CFA-induced inflammatory pain possibly associated with down-regulating phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn.

Adjuvants, Pharmaceutic ; pharmacology ; Animals ; Electroacupuncture ; methods ; Male ; Pain ; chemically induced ; metabolism ; Phosphorylation ; Posterior Horn Cells ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism