Abstract:
:Monoclonal antibodies against GD(2) ganglioside, such as ch14.18, the human-mouse chimeric antibody, have been shown to be effective for the treatment of neuroblastoma. However, treatment is associated with generalized, relatively opiate-resistant pain. We investigated if a point mutation in ch14.18 antibody (hu14.18K332A) to limit complement-dependent cytotoxicity (CDC) would ameliorate the pain behavior, while preserving antibody-dependent cellular cytotoxicity (ADCC). In vitro, CDC and ADCC were measured using europium-TDA assay. In vivo, allodynia was evaluated by measuring thresholds to von Frey filaments applied to the hindpaws after injection of either ch14.18 or hu14.18K332 into wild type rats or rats with deficient complement factor 6. Other rats were pretreated with complement factor C5a receptor antagonist and tested following ch14.18 injection. The mutation reduces the antibody's ability to activate complement, while maintaining its ADCC capabilities. Injection of hu14.18K322 (1 or 3mg/kg) produced faster resolving allodynia than that engendered by ch14.18 (1mg/kg). Injection of ch14.18 (1mg/kg) into rats with C6 complement deficiency further reduced antibody-induced allodynia, while pre-treatment with complement factor C5a receptor antagonist completely abolished ch14.18-induced allodynia. These findings showed that mutant hu14.18 K322 elicited less allodynia than ch14.18 and that ch14.18-elicited allodynia is due to activation of the complement cascade: in part, to formation of membrane attack complex, but more importantly to release of complement factor C5a. Development of immunotherapeutic agents with decreased complement-dependent lysis while maintaining cellular cytotoxicity may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of therapeutic antibodies.
journal_name
Painjournal_title
Painauthors
Sorkin LS,Otto M,Baldwin WM 3rd,Vail E,Gillies SD,Handgretinger R,Barfield RC,Yu HM,Yu ALdoi
10.1016/j.pain.2010.01.024subject
Has Abstractpub_date
2010-04-01 00:00:00pages
135-142issue
1eissn
0304-3959issn
1872-6623pii
00006396-201004000-00021journal_volume
149pub_type
杂志文章相关文献
PAIN文献大全abstract::A 1-year follow-up of two preadolescent age cohorts with musculoskeletal pain at least once a week was conducted to analyze predictive factors for the persistence of musculoskeletal pain. Of the 564 children with pain at baseline, representing one third of the sample studied, 515 (91.3%) could be followed and 452 (80....
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/S0304-3959(98)00083-9
更新日期:1998-07-01 00:00:00
abstract:ABSTRACT:The purpose of our work was to determine the role of nonopioid peptides derived from opioid prohormones in sensory hypersensitivity characteristics of neuropathic pain and to propose a pharmacological approach to restore the balance of these endogenous opioid systems. Nonopioid peptides may have a pronocicepti...
journal_title:Pain
pub_type: 杂志文章
doi:10.1097/j.pain.0000000000002045
更新日期:2021-02-01 00:00:00
abstract::A wide range of environmental stimuli have been shown to induce antinociception. Investigation of the brain regions contributing to environmentally induced antinociception (EIA) has focused primarily on the effect of disrupting neural transmission at various CNS sites. In contrast, the present study analyzed changes i...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/0304-3959(93)90108-2
更新日期:1993-01-01 00:00:00
abstract::Tri-cyclic antidepressants (TCAs) have been widely used in treating major depressive disorders. Recent studies further demonstrated that TCAs have potent sodium channel blocking effect, and amitriptyline, one of the TCAs, has a potent spinal anesthetic effect. The aim of the study was to evaluate the spinal anesthetic...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/j.pain.2004.08.003
更新日期:2004-11-01 00:00:00
abstract::Conditioned pain modulation (CPM) is a phenomenon that may be tested with a dynamic quantitative sensory test that assesses the inhibitory aspect of this pain modulatory network. Although CPM has been adopted as a clinical assessment tool in recent years, the stability of the measure has not been determined over long ...
journal_title:Pain
pub_type: 临床试验,杂志文章
doi:10.1016/j.pain.2013.06.038
更新日期:2013-12-01 00:00:00
abstract::This open prospective study evaluated the combination of initial dose titration with patient-controlled analgesia (PCA) and long-term treatment with transdermal fentanyl in 50 cancer patients requiring opioids for severe pain. The delivery rate of the first transdermal therapeutic system (TTS) was calculated from the ...
journal_title:Pain
pub_type: 临床试验,杂志文章
doi:10.1016/s0304-3959(96)03254-x
更新日期:1997-01-01 00:00:00
abstract::The objective of this study was to examine which factors during pregnancy and postpartum predict pelvic girdle pain (PGP) at 12 weeks postpartum among working women. A total of 548 Dutch pregnant employees were recruited in 15 companies, mainly health care, child care, and supermarkets. The definition of PGP was any p...
journal_title:Pain
pub_type: 杂志文章,多中心研究
doi:10.1016/j.pain.2012.08.003
更新日期:2012-12-01 00:00:00
abstract::Humans require the ability to discriminate intensities of noxious stimuli to avoid future harm. This discrimination process seems to be biased by an individual's attention to pain and involves modulation of the relative intensity differences between stimuli (ie, Weber fraction). Here, we ask whether attention networks...
journal_title:Pain
pub_type: 杂志文章
doi:10.1097/j.pain.0000000000001086
更新日期:2018-02-01 00:00:00
abstract::Substance P (SP) is released from primary afferent fibers in response to nociceptive stimuli. Capsaicin, which produces an initial hyperalgesic response followed by persistent antinociception, also elicits release of SP from primary afferent fibers. Capsaicin pretreatment decreases the content and release of SP from p...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/s0304-3959(97)03376-9
更新日期:1997-07-01 00:00:00
abstract::Animal and human studies indicate that electrical stimulation of dorsal root ganglion (DRG) neurons may modulate neuropathic pain signals. ACCURATE, a pivotal, prospective, multicenter, randomized comparative effectiveness trial, was conducted in 152 subjects diagnosed with complex regional pain syndrome or causalgia ...
journal_title:Pain
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/j.pain.0000000000000814
更新日期:2017-04-01 00:00:00
abstract::Indicators of persistent pain in preterm neonates are poorly defined. In the setting of a double blind, placebo-controlled trial investigating morphine use in ventilated preterm infants (NEOPAIN Trial) we aimed to identify factors that may be useful in assessing persistent pain. Twenty-two babies (morphine 12; placebo...
journal_title:Pain
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.pain.2006.03.019
更新日期:2006-09-01 00:00:00
abstract::The present study examined the role of catastrophizing in predicting levels of pain and disability in a sample of individuals who had sustained soft-tissue injuries to the neck, shoulders or back following work or motor vehicle accidents. Participants were 86 (27 men, 59 women) consecutive referrals to the Atlantic Pa...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/S0304-3959(98)00097-9
更新日期:1998-09-01 00:00:00
abstract::The existence of prostaglandin (PG) receptors in the spinal cord has been demonstrated, but their role in sensory processing is not yet well defined. PGE1 is widely used clinically as a vasodilator. The present study was designed to investigate the effects of intrathecally administered PGE1 on the transmission of diff...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/0304-3959(95)00055-0
更新日期:1995-12-01 00:00:00
abstract::Pro-inflammatory cytokine production after nociceptive stimuli is pivotal for hyperalgesia. As macrophage migration inhibitory factor (MIF), a pleiotropic cytokine produced mainly by nonneuronal tissue, has been involved in the regulation of neuronal functions, herein we examined the role for MIF in formalin-induced i...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/j.pain.2009.11.011
更新日期:2010-02-01 00:00:00
abstract::We investigated the role of endogenous opioid systems in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). We compared the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, in a randomized, do...
journal_title:Pain
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.pain.2010.10.032
更新日期:2011-02-01 00:00:00
abstract::Anxiety has been described as an important comorbidity in patients suffering from chronic pain. However, in animals the connection between persistent pain and anxiety has hardly been investigated. Therefore, in the current study it was assessed whether chronic pain also causes anxiety-like behaviour in animals and if ...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/j.pain.2008.05.003
更新日期:2008-10-15 00:00:00
abstract::Spasticity is a major clinical manifestation of spinal cord injury and upper motor neuron syndrome. ...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/s0304-3959(99)00255-9
更新日期:2000-03-01 00:00:00
abstract::Venlafaxine hydrochloride (Effexor) is a structurally novel antidepressant that inhibits reuptake of 5-hydroxytryptamine and noradrenaline, but unlike the older antidepressants, has few side-effects. The objective of this study was to determine whether venlafaxine relieves thermal hyperalgesia in rats with neuropathic...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/S0304-3959(96)03223-X
更新日期:1996-11-01 00:00:00
abstract::The perception of pain is highly variable. It depends on bottom-up-mediated factors like stimulus intensity and top-down-mediated factors like expectations. In the brain, pain is associated with a complex pattern of neuronal responses including evoked potentials and induced responses at alpha and gamma frequencies. Al...
journal_title:Pain
pub_type: 杂志文章,随机对照试验
doi:10.1097/01.j.pain.0000460309.94442.44
更新日期:2015-02-01 00:00:00
abstract::Since many people with chronic fatigue present with pain and many people with chronic pain present with fatigue, we tested if fatigue would enhance the response to pain in male and female mice. We further tested for the activation of brainstem nuclei by the fatigue task using c-fos as a marker. Fatigue was induced by ...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/j.pain.2009.07.001
更新日期:2010-02-01 00:00:00
abstract::Return of sensory nerve function in rat molars following cut or crush injury to the inferior alveolar nerve (IAN) was measured by observing the jaw opening reflex (JOR) response of the digastric muscle to electrical stimulation of individual molars or the gingiva. The IAN was injured from a lateral approach to the man...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/0304-3959(83)90071-4
更新日期:1983-04-01 00:00:00
abstract::The investigation of neurotransmitter systems in placebo and nocebo effects has improved our understanding of these phenomena. Yet, most studies involve healthy participants. Because the pain modulatory system may differ in healthy participants and patients with chronic pain, it is important to investigate the evidenc...
journal_title:Pain
pub_type: 杂志文章
doi:10.1097/j.pain.0000000000001682
更新日期:2020-01-01 00:00:00
abstract::We investigated the question of how cultural and linguistic backgrounds affect relationships among ratings (reported by patients with metastatic cancer) of pain's interference with such functions as activity, mood, and sleep. Multidimensional scaling (MDS) was used to analyze ratings of pain interference from a sample...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/0304-3959(96)03131-4
更新日期:1996-10-01 00:00:00
abstract::Evidence has been accumulated suggesting that a dysfunction in pain inhibitory systems, i.e. in 'diffuse noxious inhibitory controls' (DNIC)-like mechanisms, might be-amongst other factors-responsible for the development of anatomically generalized chronic pain like fibromyalgia. The aim of the present study was to lo...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/j.pain.2005.08.019
更新日期:2005-11-01 00:00:00
abstract::Postherpetic neuralgia (PHN) is a debilitating chronic pain condition, yet there is a lack of knowledge regarding underlying brain activity. Here we identify brain regions involved in spontaneous pain of PHN (n=11) and determine its modulation with Lidoderm therapy (patches of 5% lidocaine applied to the PHN affected ...
journal_title:Pain
pub_type: 临床试验,杂志文章
doi:10.1016/j.pain.2006.09.014
更新日期:2007-03-01 00:00:00
abstract::The capsaicin receptor in nociceptive neurons is a target for the sensitizing actions of algogenic inflammatory mediators. Capsaicin and potential endogenous ligands are thought not to gate this heat-activated ion channel but to sensitize it so profoundly that even room temperature can open it. We investigated the tem...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/j.pain.2004.03.033
更新日期:2004-07-01 00:00:00
abstract::A visual analog scale (VAS) method of assessing headache pain was compared with a standard categorical four-grade scale (4GS) in a randomized, placebo-controlled, double-blind, clinical trial involving 792 treated migraine outpatients who received oral rizatriptan 5 mg, sumatriptan 50 mg, or placebo for a moderate or ...
journal_title:Pain
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/S0304-3959(01)00315-3
更新日期:2001-08-01 00:00:00
abstract::Dysfunction in the motor system is a feature of persistent whiplash associated disorders. Little is known about motor dysfunction in the early stages following injury and of its progress in those persons who recover and those who develop persistent symptoms. This study measured prospectively, motor system function (ce...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/s0304-3959(02)00420-7
更新日期:2003-05-01 00:00:00
abstract::The relationship between subjective measurements of pain (pain report and threshold of sensation) and evoked potentials following painful electrical stimulation of tooth pulp was evaluated after intake of different weak analgesics. These time-response curves for the dolorimetric parameters were correlated to the in vi...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/0304-3959(82)90178-6
更新日期:1982-04-01 00:00:00
abstract::Our aim was to assess the discriminative capacity of the McGill Pain Questionnaire (MPQ) in patients with temporomandibular joint (TMJ) disorders or with myogenous facial pain (MP). The MPQ was administered to 57 TMJ and 28 MP patients who were also asked to assess the level of pain using the Visual Analog Scale (VAS)...
journal_title:Pain
pub_type: 杂志文章
doi:10.1016/S0304-3959(00)00461-9
更新日期:2001-04-01 00:00:00