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Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain.
Navratilova E, Xie J, Meske D, Qu C, Morimura K, Okun A, Arakawa N, Ossipov M, Fields H, Porreca F (2015) Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain. J Neurosci 35:7264-7271. doi: 10.1523/JNEUROSCI.3862-14.2015
Summary: There are a number of neuronal circuits involved in the processing of pain, including those that control somatosensory, affective, and cognitive aspects of pain perception. Opioid signaling in the anterior cingulate cortex (ACC) plays a part in pain modulation – this area has also been implicated in the encoding of pain aversiveness. In order to examine the neuronal mechanisms of pain relief and the following reward, the authors of this paper administered 48 ng of Dermorphin-SAP (Cat. #IT-12) into the rostral ACC of rats. Saporin (Cat. #PR-01) was used as a control. The results illuminate the opioid pathway during pain treatment, and the dependence of nucleus accumbens dopaminergic transmission on upstream ACC opioid circuits during pain processing.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
TRPV1 expression level in isolectin B₄-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity.
Ono K, Ye Y, Viet C, Dang D, Schmidt B (2015) TRPV1 expression level in isolectin B₄-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity. J Neurophysiol 113:3345-3355. doi: 10.1152/jn.00973.2014
Summary: In order to determine whether IB4-positive trigeminal sensory neurons affect pain sensitivity, the authors administered 2 μg of rIB4-SAP (Cat. #IT-10) to the right infraorbital foramen. Saporin (Cat. #PR-01) was used as a control.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Individual differences in acute pain-induced endogenous analgesia predict time to resolution of postoperative pain in the rat.
Peters C, Hayashida K, Suto T, Houle T, Aschenbrenner C, Martin T, Eisenach J (2015) Individual differences in acute pain-induced endogenous analgesia predict time to resolution of postoperative pain in the rat. Anesthesiology 122:895-907. doi: 10.1097/ALN.0000000000000593
Summary: The authors investigated the relationship between preoperative Conditioned Pain Modulation (CPM) and the time course of recovery from surgery. CPM was evaluated using forepaw capsaicin injections into rats. During the study, lesioned rats received 5-μg intrathecal injections of anti-DBH-SAP (Cat. #IT-03), followed 14 days later by a partial L5 spinal nerve ligation surgery. Mouse-IgG-SAP (Cat. #IT-18) was used as a control. CPM was partially blocked in the lesioned animals, suggesting descending noradrenergic signaling is important in the time course of recovery from surgery.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors.
Devesa I, Ferrándiz-Huertas C, Mathivanan S, Wolf C, Luján R, Changeux J, Ferrer-Montiel A (2014) αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors. Proc Natl Acad Sci U S A 111:18345-18350. doi: 10.1073/pnas.1420252111
Summary: The sensitization of transient receptor potential vanilloid 1 (TRPV1) can lead to the development and maintenance of chronic pathological pain conditions. In this work the authors determined that TRPV1 receptors use membrane insertion mechanisms in order to potentiate neuronal excitability. In order to specifically link this activity to peptidergic neurons the authors treated rat primary dorsal root ganglion cultures with 10 mM rIB4-SAP (Cat. #IT-10) to deplete the non-peptidergic neurons.
Related Products: IB4-SAP (Cat. #IT-10)
Treatment considerations for cancer pain: A global perspective.
Pergolizzi J, Gharibo C, Ho K (2015) Treatment considerations for cancer pain: A global perspective. Pain Pract 15:778-792. doi: 10.1111/papr.12253
Summary: This review discusses the treatment of cancer pain, addressing various aspects of the overall picture, such as early pain treatment to reduce central sensitization and chronic pain, pain assessment tools, and guidelines for treating specific populations of patients. Some of the current tools for pain management are discussed, including SP-SAP, which is currently in clinical trials as a cancer pain therapeutic.
Related Products: SP-SAP (Cat. #IT-07)
Spinal antinociceptive effect of gastrin releasing peptide (GRP) via GABAergic inhibitory interneurons expressing the GRP receptor (GRPR)
Akiyama T, Tominaga M, Davoodi A, Nagamine M, Takamori K, Carstens MI, Carstens E (2014) Spinal antinociceptive effect of gastrin releasing peptide (GRP) via GABAergic inhibitory interneurons expressing the GRP receptor (GRPR). Neuroscience 2014 Abstracts 158.02. Society for Neuroscience, Washington, DC.
Summary: GRPR-expressing dorsal horn neurons signal itch. We investigated a role for such neurons in modulating the spinal neurotransmission of mechanical and heat pain in mice. In behavioral studies, we measured heat and mechanical paw withdrawal thresholds using Hargreaves and von Frey assays, respectively. Mice received intrathecal (it) administration of one of following (5 µL volume); bombesin (6.2 pmol), GRP (0.1 nmol), and GRPR antagonists RC-3095 (0.03 nmol) and BW2258U89 (1.5 nmol). It administration of bombesin or GRP significantly reduced both heat and mechanical withdrawal thresholds with a maximal effect 10 min post-administration. In contrast, it administration of RC-3095 and BW2258U89 significantly increased both heat and mechanical withdrawal thresholds with a maximal effect 10 min post-administration. Mice treated with it bombesin-saporin to ablate GRPR-expressing spinal neurons exhibited reduced heat and mechanical withdrawal thresholds. It GRP failed to elicit heat and mechanical hyperalgesia in these mice. In electrophysiological recordings from superficial lumbar dorsal horn neurons, either bombesin or RC-3095 was spinally applied during responses elicited by noxious mechanical or heat stimulation of the cutaneous receptive field on the hindpaw. Bombesin increased both noxious mechanical- and heat-evoked activity in bombesin-sensitive neurons, while RC-3095 decreased noxious heat-evoked activity. In bombesin-insensitive neurons, bombesin decreased both noxious mechanical- and heat-evoked activity, while RC-3095 increased both. We additionally employed a double-label strategy to investigate if GRPR-expressing dorsal horn neurons coexpressed GABA, a molecular marker of inhibitory interneurons. Approximately 10% of GRPR-positive neurons were immunopositive for GABA. These results indicate that a subset of GRPR-expressing neurons function as interneurons in a circuit that suppresses nociceptive transmission in the dorsal horn. Noxious mechanical and heat stimuli activate GRPR-expressing dorsal horn neurons. A GABAergic subset of these may serve as inhibitory interneurons that contribute to inhibition of spinal neurons signaling heat and mechanical pain. Alternatively, GRPR-expressing neurons may drive other subsets of inhibitory interneurons. The antinociceptive circuit described here can be activated by pruritogens. We propose that the relative activity in antinociceptive and antipruritic circuits within the dorsal horn modulates itch- and pain-signaling ascending neurons to result in the perception of itch or pain.
Related Products: Bombesin-SAP (Cat. #IT-40)
C1 neurons excite A5 noradrenergic neurons during hypoxia condition
Borella TL, Takakura AC, Moreira TS (2014) C1 neurons excite A5 noradrenergic neurons during hypoxia condition. Neuroscience 2014 Abstracts 168.07. Society for Neuroscience, Washington, DC.
Summary: C1 neurons activate sympathetic tone and stimulate the hypothalamic-pituitary-adrenal axis in circumstances such as pain, hypoxia or hypotension. They also innervate pontine noradrenergic cells group, including the locus coeruleus (LC) and the ventrolateral pontine catecholaminergic region (A5). Activation of C1 neurons reportedly inhibits pontine neurons; however, because these neurons are glutamatergic and have excitatory effects elsewhere, we re-examined the effect of C1 activation on pontine noradrenergic neurons (A5) using a more selective method. We examined the neuronal effects of destroying C1 catecholaminergic neurons with unilateral injection of the immunotoxin anti-dopamine beta-hydroxylase-saporin (anti-DβH-Sap) into the A5 region during hypoxic condition. Bilateral injections of anti-DβH-Sap into A5 destroyed tyrosine hydroxylase (TH) neurons but spared facial motoneurons and serotonergic neurons within the ventrolateral medulla. Hypoxia (8% O2 – 3 hours) induced a robust increase in Fos expression within the catecholaminergic C1 region of the ventrolateral medulla. On the lesioned side, Fos expression was significantly reduced (53.4 ± 17.6 vs. control: 129.8 ± 22.3 neurons) within the C1 region after hypoxia challenge. Residual Fos expression seen in lesioned side in response to hypoxia provides a basis for probing additional circuits that may be recruited in hierarchical manner in response to hypoxia. In conclusion, the C1 neurons activate the ventrolateral pontine noradrenergic neurons (A5 region) possibly via the release of glutamate from monosynaptic C1 inputs.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Preliminary results from a phase I study of substance P-saporin in terminal cancer patients with intractable pain.
Frankel AE, Nymeyer H, Lappi DA, Higgins D, Ahn C, Noe C (2014) Preliminary results from a phase I study of substance P-saporin in terminal cancer patients with intractable pain. Journal of Clinical Oncology 32:191. doi: 10.1200/jco.2014.32.31_suppl.191
Summary: Existing pain therapies are insufficient to control cancer pain in 10-15% of patients. Substance P (SP) and its receptor, neurokinin-1 (NK-1r) have been determined to play a major role in spinal transmission of chronic pain. Animal studies have demonstrated that disruption of the NK-1r pathway alleviates chronic pain caused by a variety of stimuli. The authors are conducting a Phase I clinical trial in humans (NCT02036281) assessing the ability of SP-SAP (Cat. #IT-07) to treat intractable chronic pain due to cancer. Patients have received intrathecal injections of 1, 2, or 4 µg of SP-SAP with no evidence of toxicity or neurological or cardiac abnormalities. Doses will escalate up to 90 µg.
Related Products: SP-SAP (Cat. #IT-07)
Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission.
Liu H, Yan W, Lu X, Zhang X, Wei J, Wang X, Wang T, Wu T, Cao J, Shao C, Zhou F, Zhang H, Zhang P, Zang T, Lu X, Cao J, Ding H, Zhang L (2014) Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission. Exp Neurol 261:475-485. doi: 10.1016/j.expneurol.2014.07.018
Summary: The first synapse in the pain pathway is in the spinal dorsal horn, and several sites are involved in the descending control of pain. Previous studies have suggested that cerebrospinal fluid-contacting neurons may facilitate signal transmission and substance transport between the brain parenchyma and the CSF, including processes that modulate pain transmission. The authors administered CTB-SAP (Cat. #IT-14) into the right lateral ventricle of rats. Saporin (Cat. #PR-01) was used as a control. The results indicate that the 5-HT pathway contacting the CSF is an important piece in the descending inhibitory system controlling spinal transmission of pain.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Descending controls modulate inflammatory joint pain and regulate CXC chemokine and iNOS expression in the dorsal horn.
Carr F, Géranton S, Hunt S (2014) Descending controls modulate inflammatory joint pain and regulate CXC chemokine and iNOS expression in the dorsal horn. Mol Pain 10:39. doi: 10.1186/1744-8069-10-39
Summary: Peripheral joint pathology in conditions such as osteoarthritis does not always correlate to the amount of pain experienced, indicating that chronic pain is present. The role of descending facilitation in this form of chronic pain has not been investigated. The authors examined the role of mu opioid receptor-expressing cells in the rostral vental medulla (RVM) in behavioral hypersensitivity seen in joint pain models. Rats received 1.5 pmol of Dermorphin-SAP (Cat. #IT-12) into the RVM. Lesioned animals displayed prolonged attenuation of hypersensitivity, and altered expression of several genes was detected by qPCR, indicating that descending facilitation in the RVM is involved in joint pain behavior.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)