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Formalin-induced pain-related responses in rat lacking neurokinin-1 receptor neurons in the trigeminal nucleus caudalis
Masawaki A, Sugiyo S, Shimoda T, Sakai Y, Watanabe M, Moritani M, Yoshida A, Niwa H, Takemura M (2006) Formalin-induced pain-related responses in rat lacking neurokinin-1 receptor neurons in the trigeminal nucleus caudalis. Neuroscience 2006 Abstracts 50.8. Society for Neuroscience, Atlanta, GA.
Summary: This study examines the effect of intra cisterna magna injection of substance P (SP) conjugated to saporin (SP-Sap; 5µM, 5µl) on formalin-induced pain-related behavior (PRB; face scrubbing behavior ) and c-Fos expression in the trigeminal nucleus caudalis (SpVc). In SP-Sap-treated rats, the numbers of NK-1-immunoreactive neurons in lamina I of the SpVc decreased compared with those in saline- or blank Sap-treated rats. The mean numbers ±SEM of PRB /5 min at the first phase (0-5 min after For injection) were 58.2±19.2 in the SP-Sap-treated rats, 115.6±14.0 in the saline treated rats and 86.9±45.7 in the blank-Sap-treated rats. The numbers at the quiescent period (5-10 min) were 45.2±26.3 in the SP-Sap- treated rats, 93.6±26.5 in the saline treated rats and 69.4±16.3 in the blank-Sap-treated rats. These at the former second phase (10-50 min) were 58.1±22.3 in the SP-Sap-treated rats, 133.6±26.1 in the saline treated rats and 95.8±29.6in the blank-Sap-treated rats. These at the latter second phase (55-90 min) were 7.0±5.6 in the SP-Sap-treated rats,13.7±12.4 in the saline treated rats and 10.4±22.5 in the blank-Sap-treated rats. These results indicate that formalin-induced nociceptive responses in the SP-Sap-treated rats are reduced.
Related Products: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)
Secondary hyperalgesia in the monoarthritic rat is mediated by GABA(B) and NK1 receptors of spinal dorsal horn neurons: A behavior and c-fos study.
Castro AR, Pinto M, Lima D, Tavares I (2006) Secondary hyperalgesia in the monoarthritic rat is mediated by GABA(B) and NK1 receptors of spinal dorsal horn neurons: A behavior and c-fos study. Neuroscience 141(4):2087-2095. doi: 10.1016/j.neuroscience.2006.05.048
Summary: Hallmarks of secondary hyperalgesia in a rat model of monoarthritic pain are: decreased activation of GABA(B) neurons, and increased activation of NK1r neurons. Using 10-µl injections of 1-µM SP-SAP (Cat. #IT-07) into T(13)-L(1) the workers looked at the role of each receptor. Pain thresholds increased after treatment with SP-SAP or baclofen, a selective GABA(B) receptor agonist. Fos immunoreactivity was also decreased in treated animals, indicating that both GABA(B) and NK1r are involved in secondary hyperalgesia.
Related Products: SP-SAP (Cat. #IT-07)
Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons.
Rygh LJ, Suzuki R, Rahman W, Wong Y, Vonsy JL, Sandhu H, Webber M, Hunt S, Dickenson AH (2006) Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons. Eur J Neurosci 24(3):761-772. doi: 10.1111/j.1460-9568.2006.04968.x
Summary: Long-term potentiation (LTP) has been shown to occur in sensory areas of the spinal cord. This modification of synaptic strength may be one of the mechanisms by which acute pain is transformed into chronic pain. 10 µl of 1-µM SP-SAP (Cat. #IT-07) or control saporin (Cat. #PR-01) was injected into the subarachnoid space (L4-L5) of rats. Using electrophysiological recording, immunohistochemistry, behavioral assessment, and antisense experiments, the authors demonstrate that dorsal horn neuron generation of LTP may transform acute pain into chronic pain.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
Descending facilitation from the rostral ventromedial medulla maintains visceral pain in rats with experimental pancreatitis.
Vera-Portocarrero LP, Yie JX, Kowal J, Ossipov MH, King T, Porreca F (2006) Descending facilitation from the rostral ventromedial medulla maintains visceral pain in rats with experimental pancreatitis. Gastroenterology 130(7):2155-2164. doi: 10.1053/j.gastro.2006.03.025
Summary: Here the authors investigated the role of ascending or descending pathways in the mediation of pain caused by pancreatitis. Rats received 1.5 pmol injections of dermorphin-SAP (Cat. #IT-12) into each side of the rostral ventromedial medulla. Abdominal hypersensitivity was tested using von Frey filaments. Although the ablation of mu-opioid receptor-expressing neurons by dermorphin-SAP did not prevent the initial expression of pancreatitis pain, maintenance of this pain was absent. The data link maintenance of pancreatitis pain to descending pathways.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
Toward better pain control.
Basbaum AI, Julius D (2006) Toward better pain control. Sci Am 294(6):60-67. doi: 10.1038/scientificamerican0606-60
Summary: The authors discuss some of the advances in understanding and treating different types of pain, and specifically outline circuits, receptors, and ligands involved in pain pathways. Several treatments are described, one of which is the use of SP-SAP (Cat. #IT-07) to disrupt the chronic pain pathway in the spinal cord.
Related Products: SP-SAP (Cat. #IT-07)
Featured Article: Targeted toxins in pain
Wiley RG (2006) Featured Article: Targeted toxins in pain. Targeting Trends 7(2)
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03), Anti-SERT-SAP (Cat. #IT-23), SP-SAP (Cat. #IT-07), SSP-SAP (Cat. #IT-11), Dermorphin-SAP / MOR-SAP (Cat. #IT-12),
Safety evaluation of Intrathecal Substance P-Saporin, a targeted neurotoxin, in dogs.
Allen JW, Mantyh PW, Horais K, Tozier N, Rogers SD, Ghilardi JR, Cizkova D, Grafe MR, Richter P, Lappi DA, Yaksh TL (2006) Safety evaluation of Intrathecal Substance P-Saporin, a targeted neurotoxin, in dogs. Toxicol Sci 91(1):286-298. doi: 10.1093/toxsci/kfj143
Summary: SP-SAP (Cat. #IT-07) has been shown to reverse neuropathic pain behavior in rodents and prevent the formation of hyperalgesia. A safety study was done in beagles to further the use of this molecule as a human therapeutic. Animals received doses from 1.5-150 µg of SP-SAP as bolus intrathecal lumbar injections. Doses of 15 µg and above displayed significant loss of NK1r-expressing cells in lumbar Laminae II and I, but no adverse toxicity was observed at any dose.
Related Products: SP-SAP (Cat. #IT-07)
Facilitatory influences from the rostral ventromedial medulla (RVM) are required for pancreatic nociception
Vera-Portocarrero LP, Xie Y, King T, Lai J, Porreca F (2005) Facilitatory influences from the rostral ventromedial medulla (RVM) are required for pancreatic nociception. Neuroscience 2005 Abstracts 623.18. Society for Neuroscience, Washington, DC.
Summary: Pain is a frequent complaint of patients with pancreatitis or pancreatic cancer. An animal model of pancreatitis induced by dibutyltin dichloride (DBTC) is characterized by abdominal hypersensitivity to mechanical stimuli that appears by day 3 after induction of pancreatitis and persists for at least 10 days. We have used this model to evaluate the role of descending pain modulatory pathways from the RVM in the processing of visceral pain. Pancreatitis was induced in rats by a single tail vein injection of DBTC. Animals were monitored for mechanical sensitivity of the abdominal area as an index of pancreatic nociception using von Frey hairs applied to the surface of the abdomen and recording the frequency of withdrawals from stimulation. Six days after DBTC injection, when mechanical hypersensitivity was fully developed, lidocaine, or saline, was microinjected into the RVM. Lidocaine, but not saline, given into the RVM produced a time-related reversal of mechanical hypersensitivity which peaked by 20 min after injection in animals with pancreatitis. RVM lidocaine had no effect on rats without pancreatitis. A second group of rats received a single microinjection of the cytotoxin dermorphin-saporin into the RVM in order to ablate mu opioid receptor expressing cells that have been proposed to drive descending pain facilitation. 28 days later, the rats received DBTC and their response to mechanical stimulation was monitored daily. These rats showed mechanical hypersensitivity on day 3 after DBTC, but the sensory threshold reverted to normal level by day 6, while rats that had been pretreated with dermorphin, saporin, or water exhibited persistent mechanical hypersensitivity after DBTC out to day 10. These data suggest that a blockade of the descending input from the RVM by lidocaine is sufficient to block the pancreatitis-induced visceral pain, and that the mu opioid receptor expressing cells in the RVM are critical for the persistent pain state.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
Pain facilitatory cells in the rostral ventromedial medulla coexpress opioid-μ receptors and cholecystokinin type 2 receptors
Zhang W, Gardell SE, Xie Y, Luo M, Rance NE, Vanderah TW, Porreca F, Lai J (2005) Pain facilitatory cells in the rostral ventromedial medulla coexpress opioid-μ receptors and cholecystokinin type 2 receptors. Neuroscience 2005 Abstracts 394.17. Society for Neuroscience, Washington, DC.
Summary: Pain transmission can be modulated by descending input to the spinal dorsal horn from the rostral ventromedial medulla (RVM). RVM neurons that facilitate nociception are termed “ON-cells”, which are inhibited by mu-opioids, suggesting that they express opioid mu receptors (MOR). Focal application of cholecystokinin (CCK8(s)) into the RVM elicits acute thermal and tactile hypersensitivity and induces ON-cell activity. In situ hybridization using riboprobes for either rat MOR or rat cholecystokinin type-2 receptor (CCK-2) confirms the expression of these receptors in the RVM. Pretreatment with a toxin conjugate, CCK8(s)-saporin results in a significant loss of CCK-2 positive cells in the RVM, concomitant with a blockade of CCK8(s) induced hyperalgesia. The pretreatment also significantly reduces the number of neurons labeled for MOR in the RVM, suggesting that MOR and CCK-2 may be co-localized in some RVM cells. Consistent with these data, similar pretreatment with the toxin conjugate, dermorphin-saporin, which selectively targets MOR expressing neurons, significantly reduces the number of MOR labeled cells in the RVM, blocks RVM CCK8(s) induced hyperalgesia and reduces the number of CCK-2 positive cells in the RVM. In situ hybridization using 35S-labeled CCK-2 riboprobes and Digoxigenin-labeled MOR riboprobes shows that over 80% of labeled RVM neurons co-express both MOR and CCK-2, ~15% express only CCK-2, and very few cells express only MOR. These findings represent the first direct demonstration of the phenotype of pain facilitatory neurons in the RVM. Together with previous studies showing that RVM CCK-2 antagonists reverse nerve injury-induced pain, this phenotype provides strong support for the view that endogenous CCK is a critical mediator of the descending pain facilitation, particularly in the maintenance of experimental neuropathic pain. Support Contributed By: NIDCR R01 DE016458
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), CCK-SAP (Cat. #IT-31)
Selective ablation of non-peptidergic C-fibers using IB4-saporin as a tool to identify the functional role of these fibers in pain transmission
Bailey AL, Bennett G, Ribeiro-da-Silva A (2005) Selective ablation of non-peptidergic C-fibers using IB4-saporin as a tool to identify the functional role of these fibers in pain transmission. Neuroscience 2005 Abstracts 169.14. Society for Neuroscience, Washington, DC.
Summary: Non-peptidergic primary sensory afferents represent a sub-population of unmyelinated C-fibres implicated in the transmission of pain-related information. Evidence indicates that these afferents play a role in pain transmission distinct from peptidergic afferents. However, their exact function in pain signalling is unknown. Investigating alterations in pain behaviours and changes in neurotransmitter and receptor expression in the absence of these sensory afferents may provide some insight into their relative importance in acute and chronic pain conditions. We therefore examined the functional consequences of the selective ablation of non-peptidergic fibres in numerous models of acute pain using Isolectin B4 conjugated to saporin (IB4-SAP). Unilateral injection of IB4-SAP into the sciatic nerve resulted in the selective ablation of IB4-positive neurons in the ipsilateral dorsal root ganglion (DRG). Examination of the central terminals of non-peptidergic primary afferents in the dorsal horn revealed the near complete loss of IB4-positive, P2X3 immunoreactive (IR) varicosities. Moreover, there were marked decreases in TRPV1-IR and substance P (SP-IR) with no change in calcitonin-gene-related peptide (CGRP). Examination of a marker of inhibitory interneurons revealed no changes in GAD-IR. Behavioural analysis showed that IB4-SAP treatment had no effect on acute thermal sensitivity, acute mechanical or cold sensitivity. In an animal model of acute inflammation, IB4-SAP treatment had no effect on inflammatory heat hyperalgesia or mechanical allodynia. However, animals treated with IB4-SAP showed attenuated heat hyperalgesia induced by capsaicin 30 and 60 minutes post-injection. Data relative to acute nociceptive thresholds after other chemical stimuli will be presented. These data indicate that non-peptidergic fibres are minimally involved in acute and inflammatory pain, and may play a more prominent role in high threshold thermal sensation.
Related Products: IB4-SAP (Cat. #IT-10)