Inflammatory pain impacts adversely on the quality of life patients, often resulting in motor disabilities. Therefore, we studied effect peripheral inflammation induced by intraplantar administration complete Freund's adjuvant (CFA) mice a particular form voluntary locomotion, wheel running, as an index mobility impairment produced pain. The distance traveled over 1 hour free access to activity wheels decreased significantly response hind paw inflammation, peaking 24 hours after CFA...

The primary afferent nociceptor was used as a model system to study mechanisms of pain induced by chronic opioid administration. Repeated intradermal injection the selective mu-opioid receptor (MOR) agonist DAMGO mechanical hyperalgesia and marked prolongation prostaglandin E₂ (PGE₂) hyperalgesia, key feature hyperalgesic priming. However, in contrast prior studies priming receptor-mediated (i.e., TNFα, NGF, or IL-6 receptor) direct activation protein kinase Cε (PKCε),...

The present study evaluated the role of N-methyl-D-aspartate receptors (NMDARs) expressed in dorsal root ganglia (DRG) inflammatory sensitization peripheral nociceptor terminals to mechanical stimulation. Injection NMDA into fifth lumbar (L5)-DRG induced hyperalgesia rat hind paw with a profile similar that intraplantar injection prostaglandin E2 (PGE2), which was significantly attenuated by NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) L5-DRG. Moreover, blockade DRG AMPA...

Hyperalgesic priming, a form of neuroplasticity in nociceptors, is model the transition from acute to chronic pain rat, which involves signaling site an tissue insult vicinity peripheral terminal nociceptor its cell body that, turn, induces signal that travels back mediate marked prolongation prostaglandin E2-induced hyperalgesia. In present experiments, we studied underlying mechanisms and compared them nerve terminal. Injection cell-permeant cAMP analog, 8-bromo cAMP, into dorsal root...

It is well established that dorsal root ganglion (DRG) cells synthesize prostaglandin. However, the role prostaglandin plays in inflammatory hyperalgesia of peripheral tissue has not been established. Recently, we have successfully a technique to inject drugs (3 μL) directly into L5-DRG rats, allowing vivo identification DRG cell-derived COX-1 and COX-2 play development tissue. IL-1β (0.5 pg) or carrageenan (100 ng) was administered L5-peripheral field rat hindpaw mechanical evaluated after...

Hyperalgesic priming, an estrogen dependent model of the transition to chronic pain, produced by agonists at receptors that activate protein kinase C epsilon (PKCε), occurs in male but not female rats. However, activation second messengers downstream PKCε, such as ryanodine receptor, induces priming both sexes. Since regulates intracellular calcium, we investigated interaction between and susceptibility develop females. The lowest dose able induce females (1 pg) is 1/100,000(th) needed males...

We studied, in male Sprague Dawley rats, the role of cognate hyaluronan receptor, CD44 signaling antihyperalgesia induced by high molecular weight (HMWH). Low (LMWH) acts at both peptidergic and nonpeptidergic nociceptors to induce mechanical hyperalgesia that is prevented intrathecal oligodeoxynucleotide antisense mRNA, which also prevents a receptor agonist, A6. Ongoing LMWH A6 are reversed HMWH. HMWH reverses diverse pronociceptive mediators, prostaglandin E 2 , epinephrine, TNFα,...

In addition to analgesia, opioids produce opioid-induced hyperalgesia (OIH) and neuroplasticity characterized by prolongation of inflammatory-mediator-induced (hyperalgesic priming). We evaluated the hypothesis that priming induced are mediated similar nociceptor mechanisms. male rats, we first role Toll-like receptor 4 (TLR4) in OIH systemic low-dose morphine (LDM, 0.03 mg/kg). Intrathecal oligodeoxynucleotide antisense TLR4 mRNA (TLR4 AS-ODN) prevented prostaglandin E₂ (priming)...

Progress in the development of effective chemotherapy is producing a growing population patients with acute and chronic painful chemotherapy-induced peripheral neuropathy (CIPN), serious treatment-limiting side effect for which there currently no US Food Drug Administration-approved treatment. CIPNs induced by diverse classes drugs have remarkably similar clinical presentations, leading to suggestion they share underlying mechanisms. Sensory neurons immune cells ability detect damage...

Hyperalgesic priming, a model of pain chronification in the rat, is mediated by ryanodine receptor-dependent calcium release. Although induces priming both sexes, females are 5 orders magnitude more sensitive, an estrogen receptor α (EsRα)-dependent mechanism. An inositol 1,4,5-triphosphate (IP 3 ) inhibitor prevented induction ryanodine. For IP induced were also sensitive. -induced was pretreatment with inhibitors sarcoendoplasmic reticulum ATPase and receptor. Antisense to EsRα low-dose...

We previously developed a model of opioid-induced neuroplasticity in the peripheral terminal nociceptor that could contribute to hyperalgesia, type II hyperalgesic priming. Repeated administration mu-opioid receptor (MOR) agonists, such as DAMGO, at nociceptor, induces long-lasting plasticity expressed, prototypically hyperalgesia and prolongation prostaglandin E2-induced hyperalgesia. In this study, we evaluated mechanisms involved maintenance Opioid antagonist, naloxone, induced...

Abstract Chemotherapy-induced neuropathic pain is a serious adverse effect of chemotherapeutic agents. Clinical evidence suggests that stress risk factor for development and/or worsening chemotherapy-induced peripheral neuropathy (CIPN). We evaluated the impact and axis mediators on paclitaxel CIPN in male female rats. Paclitaxel produced mechanical hyperalgesia, over 4-day course administration, peaking by day 7, still present 28, with no significant difference between hyperalgesia was...

The ability of nanoassisted laser desorption-ionization mass spectrometry (NALDI-MS) imaging to provide selective chemical monitoring with proper spatial distribution lipid profiles from tumor tissues after plate imprinting has been tested. NALDI-MS identified and mapped several potential biomarkers in a murine model melanoma (inoculation B16/F10 cells). It also confirmed that the vivo treatment bearing mice synthetic supplement containing phosphoethanolamine (PHO-S) promoted an accentuated...

Systemic fentanyl induces hyperalgesic priming, long-lasting neuroplasticity in nociceptor function characterized by prolongation of inflammatory mediator hyperalgesia. To evaluate priming at both terminals, we studied, male Sprague Dawley rats, the effect local administration agents that reverse type I (protein translation) or II [combination Src and mitogen-activated protein kinase (MAPK)] priming. At central terminal, induced systemic, intradermal, intrathecal was reversed combination...

We have recently described a novel form of hyperalgesic priming (type II) induced by agonists at two clinically important Gi-protein-coupled receptors (Gi-GPCRs), mu-opioid and A1-adenosine. Like mu-opioids, the antimigraine triptans, which act 5-HT1B/D Gi-GPCRs, been implicated in pain chronification. determined whether sumatriptan, prototypical agonist, produces type II priming. Characteristic priming, intradermal injection sumatriptan (10 ng) change nociceptor function such that...

Peripheral inflammatory hyperalgesia depends on the sensitization of primary nociceptive neurons. Inflammation drives molecular alterations not only locally but also in dorsal root ganglion (DRG) where interleukin-1 beta (IL-1β) and purinoceptors are upregulated. Activation P2X7 by ATP is essential for IL-1β maturation release. At DRG, P2X7R expressed satellite glial cells (SGCs) surrounding sensory neurons soma. Although SGCs have no projections outside ganglia these affect pain signaling...

In Brief We have recently shown that repeated exposure of the peripheral terminal primary afferent nociceptor to mu-opioid receptor (MOR) agonist DAMGO ([D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin acetate salt) induces a model transition chronic pain we termed type II hyperalgesic priming. Similar I priming, there is markedly prolonged response subsequent administration proalgesic cytokines, prototypically prostaglandin E2 (PGE2). However, priming differs from in being rapidly induced, protein...

Cannabinoid system is a potential target for pain control. receptor 1 (CB1) activation play role in the analgesic effect of cannabinoids once it expressed primary afferent neurons. This study investigates whether anti-hyperalgesic CB1 involves P2X3 Mechanical hyperalgesia was evaluated by electronic von Frey test. using anandamide or ACEA, non-selective selective agonists, respectively; AM251, antagonist, and antisense ODN receptor. Calcium imaging assay performed to α,β-meATP-responsive...

Opioid-induced hyperalgesia (OIH) is a serious adverse event produced by opioid analgesics. Lack of an in vitro model has hindered study its underlying mechanisms. Recent evidence implicated role nociceptors OIH. To investigate the cellular and molecular mechanisms OIH nociceptors, vitro, subcutaneous administration analgesic dose fentanyl (30 μg/kg, s.c.) was performed vivo male rats. Two days later, when administered intradermally (1 μg, i.d.), vicinity peripheral nociceptor terminals, it...