Menachem Hanani

• Ph.D.
• Hebrew University of Jerusalem

Chronic pain is a global health problem with major socioeconomic implications. Drug therapy for chronic pain is limited, prompting search for non-pharmacological treatments. One such approach is physical exercise, which has been found to be beneficial for numerous health issues. Research in recent years has yielded considerable evidence for the ana...

Cisplatin and oxaliplatin are Pt(II) anticancer agents that are used to treat several cancers, usually in combination with other drugs. Their efficacy is diminished by dose-limiting peripheral neuropathy (PN) that affects ∼70% of patients. PN is caused by selective accumulation of the platinum drugs in the dorsal root ganglia (DRG), which overexpre...

Satellite glial cells (SGCs) are the main type of glial cells in sensory ganglia. Animal studies have shown that these cells play essential roles in both normal and disease states. In a large number of pain models, SGCs were activated and contributed to the pain behavior. Much less is known about SGCs in humans, but there is emerging recognition th...

Neurons in sensory ganglia are wrapped completely by satellite glial cells (SGCs). One putative function of SGCs is to regulate the neuronal microenvironment, but this role has received only little attention. In this study we investigated whether the SGC envelope serves a barrier function and how SGCs may control the neuronal microenvironment. We s...

The effects of aging on the nervous system are well documented. However, most previous studies on this topic were performed on the central nervous system. The present study was carried out on the dorsal root ganglia (DRGs) of mice, and focused on age-related changes in DRG neurons and satellite glial cells (SGCs). Intracellular electrodes were used...

The purinergic system plays an important role in pain transmission. Recent studies have suggested that activation of P2-purinergic receptors (P2Rs) may be involved in neuron-satellite glial cell (SGC) interactions in the dorsal root ganglia (DRG), but the details remain unclear. In DRG, P2X7R is selectively expressed in SGCs, which closely surround...

Emerging research indicates that physical activity can ameliorate chronic pain, but the underlying mechanisms are still largely obscure. In particular, little is known on the mechanisms behind exercise-induced analgesia in the setting of inflammatory pain. In our previous studies on systemic inflammation in mice using lipopolysaccharide (LPS) admin...

Itch (pruritus) is a common chronic condition with a lifetime prevalence of over 20%. The mechanisms underlying itch are poorly understood, and its therapy is difficult. There is recent evidence that following nerve injury or inflammation, intercellular communications in sensory ganglia are augmented, which may lead to abnormal neuronal activity, a...

Injury or inflammation in the peripheral branches of neurons of sensory ganglia causes changes in neuronal properties, including excessive firing, which may underlie chronic pain. The main types of glial cell in these ganglia are satellite glial cells (SGCs), which completely surround neuronal somata. SGCs undergo activation following peripheral le...

Primary sensory neurons in dorsal root ganglia (DRG) are wrapped by satellite glial cells (SGCs), and neuron-SGC interaction may affect somatosensation, especially nociceptive transmission. P2-purinergic receptors (P2Rs) are key elements in the two-way interactions between DRG neurons and SGCs. However, because the cell types are in such close prox...

Astroglia are neural cells, heterogeneous in form and function, which act as supportive elements of the central nervous system; astrocytes contribute to all aspects of neural functions in health and disease. Through their highly ramified processes, astrocytes form close physical contacts with synapses and blood vessels, and are integrated into func...

No disease-modifying therapy is currently available for Parkinson’s disease (PD), the second most common neurodegenerative disease. The long nonmotor prodromal phase of PD is a window of opportunity for early detection and intervention. However, we lack the pathophysiological understanding to develop selective biomarkers and interventions. By using...

Neurons and satellite glial cells (SGCs) in sensory ganglia maintain bidirectional communications that are believed to be largely mediated by chemical messengers. Nerve injury leads to SGC activation, which was proposed to be mediated by nitric oxide (NO) released from active neurons, but evidence for this is lacking. Here we tested the idea that i...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Satellite glial cells (SGCs) closely envelop cell bodies of neurons in sensory, sympathetic and parasympathetic ganglia. This unique organization is not found elsewhere in the nervous system. SGCs in sensory ganglia are activated by numerous types of nerve injury and inflammation. The activation includes upregulation of glial fibrillary acidic prot...

No disease modifying therapy is currently available for Parkinson's disease (PD), the second most common neurodegenerative disease. The long non-motor prodromal phase of PD is a window of opportunity for early detection and intervention. However, we lack the pathophysiological understanding to develop selective biomarkers and interventions. By deve...

Neurons in sensory, sympathetic, and parasympathetic ganglia are surrounded by satellite glial cell (SGCs). There is little information on the effects of nerve damage on SGCs in autonomic ganglia. We studied the consequences of damage to sympathetic nerve terminals by 6-hydroxydopamine (6-OHDA) on SGCs in the mouse superior cervical ganglia (Sup-CG...

Peripheral sensory ganglia contain the somata of neurons mediating mechanical, thermal, and painful sensations from somatic, visceral, and oro‐facial organs. Each neuronal cell body is closely surrounded by satellite glial cells (SGCs) that have properties and functions similar to those of central astrocytes, including expression of gap junction pr...

Abnormal neuronal activity in sensory ganglia contributes to chronic pain. There is evidence that signals can spread between cells in these ganglia, which may contribute to this activity. Satellite glial cells (SGCs) in sensory ganglia undergo activation following peripheral injury and participate in cellular communication via gap junctions and che...

Satellite glial cells (SGCs) surround the neurons in sympathetic ganglia and are believed to make important contributions to the function of the ganglia under normal and pathological conditions. It has been proposed that SGCs communicate chemically with the neurons, but little is known about their pharmacological properties and there is no informat...

Enhanced expression and function of gap junctions and pannexin (Panx) channels has been associated with both peripheral and central mechanisms of pain sensitization. At the level of the sensory ganglia, evidence includes augmented gap junction and pannexin1 expression in glial cells and neurons in inflammatory and neuropathic pain models and increa...

Endothelins (ET) are a family of highly active neuropeptides with manifold influences via ET receptors (ETR) in both the peripheral and central nervous systems. We have shown previously that satellite glial cells (SGCs) in mouse trigeminal ganglia (TG) are extremely sensitive to ET-1 in evoking [Ca2 +]in increase, apparently via ETBR activation, bu...

Drug studies in animal models have implicated pannexin1 (Panx1) in various types of pain, including trigeminal hypersensitivity, neuropathic pain and migraine. However, the tested drugs have limited specificity and efficacy so that direct evidence for Panx1 contribution to pain has been lacking. We here show that tactile hypersensitivity is markedl...

Lipopolysaccharide (LPS) has been used extensively to study neuroinflammation, but usually its effects were examined acutely (24 h <). We have shown previously that a single intraperitoneal LPS injection activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG) and altered several functional parameters in these cells for at least on...

Primary sensory neurons in the DRG play an essential role in initiating pain by detecting painful stimuli in the periphery. Tissue injury can sensitize DRG neurons, causing heightened pain sensitivity, often leading to chronic pain. Despite the functional importance, how DRG neurons function at a population level is unclear due to the lack of suita...

Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons in rodent DRG become hyperexcit...

Satellite glial cell (SGCs) in trigeminal and dorsal root ganglia are altered structurally and functionally under pathological conditions associated with chronic pain. These changes include reactive gliosis, augmented coupling by gap junctions, and increased responses to ATP via purinergic P2 receptors. Similar information for nodose ganglia (NG),...

Communications between satellite glial cells and neighboring neurons within sensory ganglia may contribute to neuropathic and inflammatory pain. To elucidate the role of satellite glial cells in chemotherapy-induced pain, we examined the effects of oxaliplatin on the gap junction-mediated coupling between these cells. We also examined whether the g...

Neuropathic pain is a very common complication in diabetes mellitus (DM), and treatment for it is limited. As DM is becoming a global epidemic it is important to understand and treat this problem. The mechanisms of diabetic neuropathic pain are largely obscure. Recent studies have shown that glial cells are important for a variety of neuropathic pa...

Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells inf...

Lowering of extracellular Ca2+-concentration from 14 X 10(-3) M to ca. 10(-6) M (using 1 mM ethyleneglycol bis (beta-aminoethylether)-N,N'-tetraacetic acid (EGTA)) results in weaker light adaptation by a 2 s light exposure and faster dark adaptation (half time 45 +/- 1%) of crayfish visual cells.

Local peripheral injury activates satellite glial cells (SGCs) in sensory ganglia, which may contribute to chronic pain. We hypothesized that systemic inflammation affects sensory ganglia like local injury. We induced systemic inflammation in mice by injecting lipopolysaccharide (LPS) intraperitoneally, and characterized SGCs and neurons in dorsal...

Sensory ganglia are essential for the transmission of sensory signals from the periphery to the central nervous system, and abnormal electrical activity in sensory neurons is a major factor in chronic pain. The main type of glial cells in these ganglia are satellite glial cells (SGCs), which surround the sensory neurons tightly. Recently it became...

Background: Chemotherapy-induced peripheral neuropathy is a serious side effect in cancer treatment, a major manifestation being neuropathic pain that can be debilitating and can reduce the quality of life of the patient. Oxaliplatin and taxol are common anti-cancer drugs that induce neuropathic pain by an unknown mechanism. We tested the hypothes...

This resource is the long-awaited new revision of the most highly regarded reference volume on glial cells, and has been completely revised, greatly enlarged, and enhanced with full color figures throughout. Neglected in research for years, it is now evident that the brain only functions in a concerted action of all the cells, namely glia and neuro...

The longitudinal muscle in the large intestine in humans and some other mammalian species is concentrated in regions known as "tenia coli." The myenteric plexus under the tenia is believed to be highly developed to control the adjacent large muscle mass, however, data on the innervation of this region are very scarce. We used whole mount preparatio...

Peripheral injury can cause abnormal activity in sensory neurons, which is a major factor in chronic pain. Recent work has shown that injury induces major changes not only in sensory neurons but also in the main type of glial cells in sensory ganglia-satellite glial cells (SGCs), and that interactions between sensory neurons and SGCs contribute to...

Hyperthermia is defined as an elevated body temperature due to failed thermoregulation. It can occur under physiological conditions such as intense exercise or due to pathology such as malignant hyperthermia and heat stroke. It has also been implicated as a cause for sudden infant death syndrome. High temperatures are also used in medical intervent...

There is immunohistochemical evidence for endothelin (ET) receptors in satellite glial cells in sensory ganglia, but there is no information on the function of these receptors. We used calcium imaging to study this question in isolated mouse trigeminal ganglia and found that satellite glial cells are highly sensitive to ET-1, with threshold at 0.05...

Introduction A very brief history of intracellular labelling techniques Methods for loading cells with LY Electrophysiological studies using LY‐filled electrodes Studying cell morphology with LY Using LY to study intercellular communication Retrograde labelling with LY Photoconversion of LY Combination of LY labelling with other methods Antibodies...

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) gained wide acceptance as the treatment of choice for selected patients with peritoneal surface malignancies. Patients tend to suffer from prolonged ileus following CRS + HIPEC, complicating their recovery. We studied the effects of hyperthermia on the intestine to ga...

Satellite glial cells (SGCs) are specialized cells that form a tight sheath around neurons in sensory ganglia. In recent years, there is increasing interest in SGCs and they have been studied in both intact ganglia and in tissue culture. Here we studied phenotypic changes in SGCs in cultured trigeminal ganglia from adult mice, containing both neuro...

A focal and transitory inflammation induced by injection of complete Freund's adjuvant (CFA) in the submandibular skin of mice elicits pain behavior that persists for several weeks after the initial inflammation has resolved. Chronic pain, assessed as tactile hypersensitivity to stimulation with von Frey filaments, was evident from 1-7 weeks follow...

Background and Objectives Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) gained wide acceptance as the treatment of choice for selected patients with peritoneal surface malignancies. Patients tend to suffer from prolonged ileus following CRS + HIPEC, complicating their recovery. We studied the effects of hyperther...

Glial cells are established as essential for many functions of the central nervous system, and this seems to hold also for glial cells in the peripheral nervous system. The main type of glial cells in most types of peripheral ganglia - sensory, sympathetic, and parasympathetic - is satellite glial cells (SGCs). These cells usually form envelopes ar...

Intercellular coupling by gap junctions is one of the main features of glial cells, but very little is known about this aspect of satellite glial cells (SGCs) in sympathetic ganglia. We used the dye coupling method to address this question in both a prevertebral ganglion (superior mesenteric) and a paravertebral ganglion (superior cervical) of mice...

Astrocytes communicate with neurons, endothelial and other glial cells through transmission of intercellular calcium signals. Satellite glial cells (SGCs) in sensory ganglia share several properties with astrocytes, but whether this type of communication occurs between SGCs and sensory neurons has not been explored. In the present work we used cult...

Recent findings highlight the participation of central glial cells in chronic pain, but less is known of a comparable role for satellite glial cells (SGCs), in dorsal root ganglia (DRG). Our previous work showed that sciatic nerve axotomy augmented SGC coupling by gap junctions. The aim of the present research was to find out whether similar change...

Peripheral injuries can lead to sensitization of neurons in dorsal root ganglia (DRGs), which can contribute to chronic pain. The neurons are sensitized by a combination of physiological and biochemical changes, whose full details are still obscure. Another cellular element in DRGs are satellite glial cells (SGCs), which surround the neurons, but l...

Glycogen represents the major brain energy reserve though its precise functions are still under debate. Glycogen has also been found in different cell types of the enteric nervous system (ENS), the largest and most complex component of the peripheral nervous system. In the present work we have demonstrated, by application of isozyme-specific antibo...

Intussusception (IS), an invagination of a portion of the intestine into itself, has recently attracted considerable interest after the withdrawal of a rotavirus vaccine because of reports on increased risk of IS shortly after vaccination. The present study was designed to shed further light on the mechanism of IS formation and its prevention. Intu...

Aquaporin-4 is a water channel predominantly found in astrocytes in the central nervous system and is believed to play a critical role in the formation and maintenance of the blood-brain barrier and in water secretion from the brain. As enteric glial cells were found to share several similarities with astrocytes, we hypothesized that enteric glia m...

The submucosal plexus regulates various activities of the gastrointestinal mucosa. As the submucosa in the human colon contains adipose tissue we hypothesized that submucosal neurons might also innervate this tissue. We stained submucosal nerves for the enzyme NADPH-diaphorase, which is a marker for nitric oxide synthase-containing nerves. This res...

Soybeans have been shown to have numerous health benefits, but the underlying mechanisms are poorly understood. The aim of this study was to characterize some pharmacologic properties of active substances in aqueous soy extract. The pharmacologic actions of the extract were tested by measuring mechanical activity of isolated guinea-pig ileum in an...

Neurons in dorsal root ganglia (DRG) are surrounded by an envelope of satellite glial cells (SGCs). Little is known about SGC physiology and their interactions with neurons. In this work, we investigated changes in mouse DRG neurons and SGC following the induction of inflammation in the hind paw by the injection of complete Freund's adjuvant (CFA)....

Glial cells in both central and peripheral nervous systems are connected by gap junctions, which allow electrical and metabolic coupling between them. In spite of the great current interest in aging of the nervous system, the effect of aging on glial cell coupling received little attention. We examined coupling between satellite glial cells in muri...

Ablation of the myenteric plexus in mouse colon with the detergent benzalkonium chloride (BAC) is followed by considerable recovery of the nerves, indicating that this plexus is capable of regeneration and has plasticity. Interstitial cells of Cajal (ICC) are closely associated with enteric nerves, and the acquisition and maintenance of their adult...

There is evidence that sensitization of neurons in dorsal root ganglia (DRG) may contribute to pain induced by intestinal injury. We hypothesized that obstruction-induced pain is related to changes in DRG neurons and satellite glial cells (SGCs). In this study, partial colonic obstruction was induced by ligation. The neurons projecting to the colon...

Current information indicates that glial cells participate in all the normal and pathological processes of the central nervous system. Although much less is known about satellite glial cells (SGCs) in sensory ganglia, it appears that these cells share many characteristics with their central counterparts. This review presents information that has be...

Dorsal root ganglia (DRG) are key elements in sensory signaling under physiological and pathological conditions. Little is known about electrical coupling among cells in these ganglia. In this study, we injected the fluorescent dye Lucifer yellow (LY) into single cells to examine dye coupling in DRG. We found no dye coupling between neurons or betw...

Interstitial cells of Cajal (ICC) are essential for the normal function of the digestive tract, both as pacemakers and as intermediates between nerves and smooth muscle cells. To perform their functions ICC must be electrically coupled both among themselves and to the muscle layers. This review focuses on the role gap junctions play in coupling ICC...

Damage to peripheral nerves induces ectopic firing in sensory neurons, which can contribute to neuropathic pain. As most of the information on this topic is on dorsal root ganglia we decided to examine the influence of infra-orbital nerve section on cells of murine trigeminal ganglia. We characterized the electrophysiological properties of neurons...

Aging is believed to affect the structure and function of the enteric nervous system, but little specific information on this topic is available, particularly in humans. The aim of this study was to investigate the effect of age on the structure of myenteric ganglia in the human colon. We examined myenteric ganglia in colonic specimens obtained fro...

Familial dysautonomia (FD) is a hereditary disease of the autonomic and sensory nervous system. A prominent manifestation of FD is gastrointestinal dyscoordination, which contributes to the morbidity and mortality in FD. As the myenteric plexus is an essential factor in gastrointestinal motility control, we compared its morphology in appendices of...

Current knowledge on the morphology and physiology of interstitial cells of Cajal (ICC) is mostly based on animal studies, and information about the function of these cells in humans is scarce. There is ultrastructural evidence that ICC in the myenteric region (ICC-MP) of the small intestine of several species are connected by gap junctions, but th...

The general histological organization of the appendix, including its innervation, is believed to be generally similar to that of the large intestine. However, several authors described an unusual arrangement of the myenteric ganglia within the appendiceal muscle, but conflicting reports do not allow clear conclusions on this matter. The aim of this...

Cellular signaling via extracellular nucleotides appears to play a major role in the functioning of the peripheral nervous system. Information regarding the functional characterization of nucleotide P2 receptors or their expression pattern has been accumulating rapidly; however, very little is known regarding the distribution of ecto-nucleotidases...

Interstitial cells of Cajal (ICC) are essential for the normal function of the digestive tract, both as pacemakers and as intermediates between nerves and smooth muscle cells. To perform their functions ICC must be electrically coupled both among themselves and to the muscle layers. This review focuses on the role gap junctions play in coupling ICC...

Neurons are cells that receive, transform and propagate information. For this purpose, they are endowed with a variety of processes or other cellular compartments, dedicated to one or more of these tasks. Generally, neurons are polarized in that one pole is optimized to receive information, and the other to transmit it to targets such as other neur...

Interstitial cells in the deep muscular plexus (ICC-DMP) are thought to be essential for neurotransmission in the circular muscle. There is evidence for gap junctions within the ICC-DMP network and between ICC-DMP and muscle cells; however, there is no evidence for functional coupling via these gap junctions. In addition, the innervation of individ...

Recent reports suggest a far greater plasticity in nerve tissue than previously believed. As the digestive tract is exposed to a variety of insults, this question is relevant to enteric nerves, but little is known about their ability to recover from damage. To address this problem, we ablated the myenteric plexus of the mouse colon with the deterge...

Intestinofugal afferent neurones (IFANs) provide excitatory synaptic input to abdominal prevertebral ganglion neurones. Input is greatly reduced during blockade of nicotinic acetylcholine receptors (nAChRs) in the wall of the colon, suggesting two projection pathways: a direct pathway without synaptic interruption and an indirect pathway interrupte...

This study investigated satellite cell changes in mouse L4 and L5 spinal ganglia 14 days after unilateral transection of sciatic and saphenous nerves. The ganglia were studied under the electron microscope in single and serial sections, and by dye injection. Satellite cell responses to axon injury of the neurons with which they are associated inclu...

There is strong evidence for the presence of nucleotide (P2) receptors in sensory neurons, which might play a role in the transmission of pain signals. In contrast, virtually nothing is known about P2 receptors in satellite glial cells (SGCs), which are the main glial cells in sensory ganglia. We investigated the possibility that P2 receptors exist...

Interstitial cells of Cajal (ICC) form networks that intercalate between the enteric nervous system and smooth muscle cells and play a fundamental role in the control of gastrointestinal motility by initiating rhythmic electrical activity. In this report, we used a method to examine the physiological and morphological properties of ICC in living, i...

Erythromycin was found to stimulate motor activity in the upper gastrointestinal tract. However, in several smooth muscle preparations, it also elicited an inhibitory effect. Our aim was to study the effect of erythromycin in various human alimentary tract smooth muscles. Using force measurements, we assessed the effect of erythromycin on electrica...