Nociceptive Messages Research Articles

Short-term plasticity in the spinal nociceptive system.

Somatosensory information is delivered to neuronal networks of the dorsal horn (DH) of the spinal cord by the axons of primary afferent neurons that encode the intensity of peripheral sensory stimuli under the form of a code based on the frequency of action potential firing. The efficient processing of these messages within the DH involves frequency-tuned synapses, a phenomenon linked to their ability to display activity-dependent forms of short-term plasticity (STP). By affecting differently excitatory and inhibitory synaptic transmissions, these STP properties allow a powerful gain control in DH neuronal networks that may be critical for the integration of nociceptive messages before they are forwarded to the brain, where they may be ultimately interpreted as pain. Moreover, these STPs can be finely modulated by endogenous signaling molecules, such as neurosteroids, adenosine, or GABA. The STP properties of DH inhibitory synapses might also, at least in part, participate in the pain-relieving effect of nonpharmacological analgesic procedures, such as transcutaneous electrical nerve stimulation, electroacupuncture, or spinal cord stimulation. The properties of target-specific STP at inhibitory DH synapses and their possible contribution to electrical stimulation-induced reduction of hyperalgesic and allodynic states in chronic pain will be reviewed and discussed.

Modulation of GABAergic Synaptic Transmission by NMDA Receptors in the Dorsal Horn of the Spinal Cord.

The dorsal horn (DH) of the spinal cord is an important structure involved in the integration of nociceptive messages. Plastic changes in the properties of neuronal networks in the DH underlie the development of analgesia as well as of hyperalgesia and allodynia in acute and chronic pain states. Two key mechanisms are involved in these chronic pain states: increased electrical activities and glutamate release leading to the recruitment of NMDAr and plastic changes in the synaptic inhibition. Although: (1) the balance between excitation and inhibition is known to play a critical role in the spinal network; and (2) plastic changes in spinal excitation and inhibition have been studied separately, the relationship between these two mechanisms has not been investigated in detail. In the present work, we addressed the role of NMDA receptors in the modulation of GABAergic synaptic transmission in the DH network. Using tight-seal whole-cell recordings on adult mice DH neurons, we characterized the effect of NMDAr activation on inhibitory synaptic transmission and more especially on the GABAergic one. Our results show that, in a subset of neurons recorded in lamina II, NMDAr activation facilitates spontaneous and miniature GABAergic synaptic transmission with a target specificity on GABAergic interneurons. In contrast, NMDA reduced the mean amplitude of evoked GABAergic IPSCs. These results show that NMDAr modulate GABAergic transmission by a presynaptic mechanism of action. Using a pharmacological approach, we investigated the composition of NMDAr involved in this modulation of GABAergic synaptic transmission. We found that the NMDA-induced facilitation was mediated by the activation of NMDAr containing GluN2C/D subunits. Altogether, our results bring new insights on nociceptive information processing in the spinal cord network and plastic changes in synaptic inhibition that could underlie the development and maintenance of chronic pain.

Vision actuelle de la douleur arthrosique : comprendre la physiopathologie et l’expérience des patients pour une meilleure prise en charge

Pain is the main clinical manifestation of osteoarthritis. It is not simply a nociceptive message associated with joint destruction. In osteoarthritis, chronic pain is a disease in its own right, with several components: nociceptive, neuropathic and nociplastic. Assessment of pain intensity is a prerequisite. Adding self-questionnaires (DN4, ICOAP, OASIS…) makes it possible to screen for the different components of pain and to assess the patient experience. Ultimately, better phenotyping of osteoarthritic patients according to their pain would allow personalized treatment adapted to underlying pain mechanisms.

PKCγ interneurons, a gateway to pathological pain in the dorsal horn.

Chronic pain is a frequent and disabling condition that is significantly maintained by central sensitization, which results in pathological amplification of responses to noxious and innocuous stimuli. As such, mechanical allodynia, or pain in response to a tactile stimulus that does not normally provoke pain, is a cardinal feature of chronic pain. Recent evidence suggests that the dorsal horn excitatory interneurons that express the γ isoform of protein kinase C (PKCγ) play a critical role in the mechanism of mechanical allodynia during chronic pain. Here, we review this evidence as well as the main aspects of the development, anatomy, electrophysiology, inputs, outputs, and pathophysiology of dorsal horn PKCγ neurons. Primary afferent high-threshold neurons transmit the nociceptive message to the dorsal horn of the spinal cord and trigeminal system where it activates second-order nociceptive neurons relaying the information to the brain. In physiological conditions, low-threshold mechanoreceptor inputs activate inhibitory interneurons in the dorsal horn, which may control activation of second-order nociceptive neurons. During chronic pain, low-threshold mechanoreceptor inputs now activate PKCγ neurons that forward the message to second-order nociceptive neurons, turning thus tactile inputs into pain. Several mechanisms may contribute to opening this gate, including disinhibition, activation of local astrocytes, release of diffusible factors such as reactive oxygen species, and alteration of the descending serotoninergic control on PKCγ neurons through 5-HT2A serotonin receptors. Dorsal horn PKCγ neurons, therefore, appear as a relevant therapeutic target to alleviate mechanical allodynia during chronic pain.

Potentiation of the Glycine Response by Bisphenol A, an Endocrine Disrupter, on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Mice.

Lamina II, also called the substantia gelatinosa (SG) of the medullary dorsal horn (the trigeminal subnucleus caudalis, Vc), is thought to play an essential role in the control of orofacial nociception because it receives the nociceptive signals from primary afferents, including thin myelinated Aδ- and unmyelinated C-fibers. Glycine, the main inhibitory neurotransmitter in the central nervous system, plays an essential role in the transference of nociceptive messages from the periphery to higher brain regions. Bisphenol A (BPA) is reported to alter the morphological and functional characteristics of neuronal cells and to be an effector of a great number of ion channels in the central nervous system. However, the electrophysiological effects of BPA on the glycine receptors of SG neurons in the Vc have not been well studied. Therefore, in this study, we used the whole-cell patch-clamp technique to determine the effect of BPA on the glycine response in SG neurons of the Vc in male mice. We demonstrated that in early neonatal mice (0-3 postnatal day mice), BPA did not affect the glycine-induced inward current. However, in the juvenile and adult groups, BPA enhanced the glycine-mediated responses. Heteromeric glycine receptors were involved in the modulation by BPA. The interaction between BPA and glycine appears to have a significant role in regulating transmission in the nociceptive pathway.

The NaV1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in Adult Dorsal Root Ganglia Neurons.

Although necessary for human survival, pain may sometimes become pathologic if long-lasting and associated with alterations in its signaling pathway. Opioid painkillers are officially used to treat moderate to severe, and even mild, pain. However, the consequent strong and not so rare complications that occur, including addiction and overdose, combined with pain management costs, remain an important societal and economic concern. In this context, animal venom toxins represent an original source of antinociceptive peptides that mainly target ion channels (such as ASICs as well as TRP, CaV, KV and NaV channels) involved in pain transmission. The present review aims to highlight the NaV1.7 channel subtype as an antinociceptive target for spider toxins in adult dorsal root ganglia neurons. It will detail (i) the characteristics of these primary sensory neurons, the first ones in contact with pain stimulus and conveying the nociceptive message, (ii) the electrophysiological properties of the different NaV channel subtypes expressed in these neurons, with a particular attention on the NaV1.7 subtype, an antinociceptive target of choice that has been validated by human genetic evidence, and (iii) the features of spider venom toxins, shaped of inhibitory cysteine knot motif, that present high affinity for the NaV1.7 subtype associated with evidenced analgesic efficacy in animal models.

Kinetotheray and Massage in Lumbar Discopathy

The importance of the topic approached: by definition, lumbosacralgia is a painfully localized symptom for which it is not always possible to establish a direct relationship between the importance the patient is giving to this suffering and the anatomo-pathological changes of the spine. Somatic manifestations depend on the etiopathogenicity of the disease as well as on the psychological interpretation of the nociceptive message. The participation of these psychosomatic components is not at all negligible and it explains the spectacular improvements made by means that at first sight have nothing in common with the supposed underlying etiopathogenic pain. Lumbosacral pain located or associated with a root syndrome accounts for more than 50% of the cases occurring in physical medicine services. In all countries, the same suffering represents a temporary incapacity to work and has very high social costs. Studies show that spine pain reaches about 80% of adults, but only 20% of the cases get true vertebral pathology. Its incidence increases with age, women between 40-60 years of age being more often affected than men. These patients are not only familiar with physiotherapy, but we also find them in the rheumatology, internal medicine, neurology, neurosurgery, orthopedics ward. This dispersion between different specialist medical services can be explained to a certain extent by the diversity of the etiopathogenic factors involved in triggering the lumbosacral pain. On the other hand, there is a lack of proper health education in this area. Lumbar discopathy is characterized by back pain located in the lumbar region at some point in the patients’ life. Current studies highlight the fact that vertebral discopathy occurs more and more in younger persons. Dorso-lumbar spondylosis (dorsolombarthrosis) is the localization of the degenerative process or a developmental abnormality in the dorsal and lumbar spine, both in the discosomatic and the interapophoresis sector; there may be manifestations of diffuse osteophytosis at this level. It is frequently localized in the diartrodial mobile articular joint, which presents the articular cartilage as an important element of the joint with evolution towards functional articular agenesis in the end.

Hyperpolarization-activated channels shape temporal patterns of ectopic spontaneous discharge in C-nociceptors after peripheral nerve injury.

Neuropathic pain is thought to be mediated by aberrant impulses from sensitized primary afferents, and the temporal summation of the discharges might also influence nociceptive processing. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (Ih current) generate rhythmic activity in neurons within the central nervous system and contribute to nociceptors excitability in neuropathic pain. We searched for single fibres with ectopic spontaneous discharges from an invitro preparation in mice containing a neuroma formed in a peripheral branch of the saphenous nerve together with the undamaged branches. Both damaged (axotomized) and undamaged fibres (putative intact) developed ectopic spontaneous activity with different temporal spike trains: Clock-like, Irregular or Bursts. The Ih current blocker, ZD7288, significantly suppressed ectopic spontaneous discharges in nociceptive fibres (3/5 Aδ- and 24/31 C-units and 1 nonclassified) by 64%. Additionally, ZD7288 changed the spike patterns of 5/7 Clock-like and 3/4 Burst units to Irregular. Exogenous cAMP produced a significant ~65% increase in the ectopic firing in 5 Irregular fibres, which was restored by ZD7288. In six additional fibres (three Clock-like and three Irregular), exogenous cAMP had no further effect, but co-application with ZD7288 decreased their discharge by half. These units showed significant higher levels of discharges than the cAMP-sensitive ones. Our data suggest that HCN channels modulate ectopic spontaneous firing in C-nociceptors and shape their temporal patterns of discharge which will, ultimately, modify the nociceptive message received and processed by second-order neurons. We show an involvement of HCN channels in the modulation of ectopic spontaneous discharges from C-nociceptors. This finding exposes a mechanism of nociceptive transmission enhancement and highlights the clinical relevance of peripheral HCN blockade for spontaneous pain relief during neuropathy.

Repeated Ganglion Impar Block in a Cohort of 83 Patients with Chronic Pelvic and Perineal Pain

Background: The ganglion impar is the first pelvic ganglion of the efferent sympathetic trunk that relays pelvic and perineal nociceptive messages and therefore constitutes a therapeutic target. Objective: The objective of this single-center study was to evaluate the effectiveness of 3 repeated ganglion impar blocks in patients with chronic pelvic and perineal pain on intention-to-treat. Study Design: Retrospective single-center study. Setting: We reviewed the medical records of 83 patients with chronic refractory pelvic and perineal pain. On intention-to-treat analysis, 62 (74.7%) of the patients received 3 ganglion impar blocks. Methods: Ganglion impar block was performed with 0.75% ropivacaine via a lateral approach over the Co1-Co2 coccygeal joint with computed tomography (CT) guidance. The effectiveness of ganglion impar blocks was evaluated by visual analogue scale (VAS) before and 30 minutes after the blocks. Evaluation at least one month after the block was also performed by Patient Global Impression of Change (PGI-C). Results: A total of 220 blocks were performed, 193 (87.7%) of which were considered to be positive with immediate but transient improvement of pain by more than 50% and complete but transient pain relief after the procedure in 119 (54.1%) procedures. The variation of the VAS score before and after each block was statistically significant (P < 0.001). Similarly, the VAS score before repeated blocks was significantly improved with decreased pain intensity over time (P = 0.001). Analysis of the PGI-C one month after the block demonstrated improvement in 41% of cases in the overall population and in 43.6% of cases in the subgroup of 62 patients treated by 3 blocks. Limitations: Retrospective study, short term follow-up. Conclusions: Repeated ganglion impar blocks allowed short-term reduction of pain intensity with a moderate intermediate-term effect. Ganglion impar appears to be a useful therapeutic target to block the nociceptive message by acting on sensitization phenomena.

Traitements chirurgicaux de la névralgie trigéminale classique

Neurosurgical management of classical trigeminal neuralgia is based on three types of techniques: an “etiological” and nondestructive technique, microvascular decompression (MVD), which consists in decompressing the trigeminal nerve in the cerebello-pontine angle, where a vascular compression is frequently found at the origin of pain; percutaneous lesioning techniques (thermorhizotomy, microcompression by balloon, injection of glycerol), aimed at disrupting the transmission of the nociceptive message; and radiosurgery. During the consultation, the neurosurgeon will try to answer three questions: “Is this a trigeminal neuralgia?”; “Is it a classical form?”; and “Is it resistant to medical treatment?”. He will present to the patient the different surgical possibilities, emphasizing the “benefit/risk” balance, and propose the most adapted to his case. In a patient in good general condition, with a clear vascular compression at magnetic resonance imaging (MRI), it seems logical to discuss the first-line MVD, as this reference technique addresses the cause of classical trigeminal neuralgia and has a high probability level of good evolution on the long term. Radiosurgery can also be offered as an alternative because of its less invasiveness and morbidity (in particular, a very low rate of hypoesthesia compared to percutaneous techniques). A patient with an altered general condition or recurrence after MVD (without MRI residual vascular compression) may be referred for surgery or radiosurgery. Depending on the technique chosen, the patient should be informed that pain relief will often be “at the cost” of a hypoesthesia more or less pronounced. Between these two extreme and relatively easy cases, all intermediate situations are possible. In the absence of a randomized controlled study evaluating the different surgical techniques, the American Academy of Neurology and the European Federation of Neurological Societies admit that formal recommendations on surgical treatment cannot be made. However, these Scientific Societies indicate that (1) patients with an MVD have a longer pain-free period than other surgical techniques, at the cost of significant morbidity, reduced in teams with high activity in neuralgia and (2) radiosurgery is the technique with the least complication.

Analysis of spontaneous activity of superficial dorsal horn neurons in vitro: neuropathy-induced changes.

The superficial dorsal horn contains large numbers of interneurons which process afferent and descending information to generate the spinal nociceptive message. Here, we set out to evaluate whether adjustments in patterns and/or temporal correlation of spontaneous discharges of these neurons are involved in the generation of central sensitization caused by peripheral nerve damage. Multielectrode arrays were used to record from discrete groups of such neurons in slices from control or nerve damaged mice. Whole-cell recordings of individual neurons were also obtained. A large proportion of neurons recorded extracellularly showed well-defined patterns of spontaneous firing. Clock-like neurons (CL) showed regular discharges at ∼6Hz and represented 9% of the sample in control animals. They showed a tonic-firing pattern to direct current injection and depolarized membrane potentials. Irregular fast-burst neurons (IFB) produced short-lasting high-frequency bursts (2-5 spikes at ∼100Hz) at irregular intervals and represented 25% of the sample. They showed bursting behavior upon direct current injection. Of the pairs of neurons recorded, 10% showed correlated firing. Correlated pairs always included an IFB neuron. After nerve damage, the mean spontaneous firing frequency was unchanged, but the proportion of CL increased significantly (18%) and many of these neurons appeared to acquire a novel low-threshold A-fiber input. Similarly, the percentage of IFB neurons was unaltered, but synchronous firing was increased to 22% of the pairs studied. These changes may contribute to transform spinal processing of nociceptive inputs following peripheral nerve damage. The specific roles that these neurons may play are discussed.

Spinal cellular and network properties modulate pain perception

Through the example the modulation of pain perception by a steroid hormone, I’m going to show you a multiscale interaction between two systems of an organism. Indeed, we will see how a the endocrine system via a molecule circulating in the blood will modulate its target molecule in the nervous system that will, in turn, change cellular activities at one stage of the central nervous system that could alter the behavior of this organism.Indeed our body collects somatosensory information from our environment that will be transmitted to the central nervous system by the peripheral nervous system. Amongst these sensory information there are nociceptive sensory inputs. A nociceptive stimuli detected at the level of the skin will be relayed by the spinal cord to the cortex where it will be interpreted as pain. The dorsal horn of the spinal cord is not a mere relay of the primary nociceptive input. At the level of the superficial layers of the dorsal horn, the nociceptive inputs are processed by a network of excitatory and inhibitory neurons before being transmitted via an ascending pathway to the brain where it will be interpreted as pain. At that level nociceptive processing is tuned by GABAA receptor-mediated inhibition in the spinal cord dorsal horn. These GABAergic inhibitory postsynaptic currents (IPSCs) are known to be modulated by spinally reduced steroids.Corticosterone (CORT) is a glucocorticoid produced by adrenal glands under the control of the hypothalamic-pituitary-adrenal axis. Circulating CORT can enter the central nervous system and be reduced to neuroactive reduced steroids, which modulate GABAA receptors. In the dorsal spinal cord, GABAergic transmission modulates integration of nociceptive information. It has been shown that enhancing spinal inhibitory transmission alleviates hyperalgesia and allodynia. Therefore, the spinal neuronal network is a pivotal target to counteract pain symptoms. Thus, any increase of spinal reduced steroids production enhancing GABAergic inhibition should reduce nociceptive messages integration and pain response.Previously, it has been shown that high levels of plasma glucocorticoids give rise to analgesia. However to our knowledge nothing has been reported regarding a direct non genomic modulation of neuronal spinal activity by peripheral CORT. In the present study, we used combined in vivo and in vitro electrophysiology approaches, associated with the measure of nociceptive mechanical sensitivity and plasma corticosterone level measurement to assess the impact of circulating CORT on rat nociception. We showed that CORT plasma level elevation produced analgesia via the reduction of nociceptive fiber mediated spinal responses. CORT is spinally reduced in the neuroactive metabolite THDOC that specifically enhances lamina II GABAergic synaptic transmission. The main consequence is a reduction of lamina II network excitability reflecting a selective decrease in processing of nociceptive inputs. The depressed neuronal activity at the spinal level then in turn leads to a weaker nociceptive message transmission to supraspinal structures and hence to an alleviation of pain.

Osteoarthritis pain.

Osteoarthritis (OA) represents one of the most frequently occurring painful conditions. Pain is the major OA symptom, involving both peripheral and central neurological mechanisms. OA pain is initiated from free axonal endings located in the synovium, periosteum bone, and tendons, but not in the cartilage. The nociceptive message involves not only neuromediators and regulating factors such as neuronal growth factor (NGF) but also central modifications of pain pathways. OA pain is a mixed phenomenon where nociceptive and neuropathic mechanisms are involved in both the local and central levels. OA pain perception is influenced by multiple environmental, psychological, or constitutional factors, and OA pain intensity is not correlated with joint degradation. OA pain may present with different clinical features: constant and intermittent pain, with or without a neuropathic component, and with or without central sensitization. Finally, OA pain should be considered as a complex and not unique pain condition, where precise clinical assessment may drive specific therapeutic approaches.

Corticosterone analgesia is mediated by the spinal production of neuroactive metabolites that enhance GABAergic inhibitory transmission on dorsal horn rat neurons.

Corticosterone (CORT) is a glucocorticoid produced by adrenal glands under the control of the hypothalamic-pituitary-adrenal axis. Circulating CORT can enter the central nervous system and be reduced to neuroactive 3α5α-reduced steroids, which modulate GABAA receptors. In the dorsal spinal cord, GABAergic transmission modulates integration of nociceptive information. It has been shown that enhancing spinal inhibitory transmission alleviates hyperalgesia and allodynia. Therefore, the spinal neuronal network is a pivotal target to counteract pain symptoms. Thus, any increase in spinal 3α5α-reduced steroid production enhancing GABAergic inhibition should reduce nociceptive message integration and the pain response. Previously, it has been shown that high levels of plasma glucocorticoids give rise to analgesia. However, to our knowledge, nothing has been reported regarding direct non-genomic modulation of neuronal spinal activity by peripheral CORT. In the present study, we used combined in vivo and in vitro electrophysiology approaches, associated with measurement of nociceptive mechanical sensitivity and plasma CORT level measurement, to assess the impact of circulating CORT on rat nociception. We showed that CORT plasma level elevation produced analgesia via a reduction in C-fiber-mediated spinal responses. In the spine, CORT is reduced to the neuroactive metabolite allotetrahydrodeoxycorticosterone, which specifically enhances lamina II GABAergic synaptic transmission. The main consequence is a reduction in lamina II network excitability, reflecting a selective decrease in the processing of nociceptive inputs. The depressed neuronal activity at the spinal level then, in turn, leads to weaker nociceptive message transmission to supraspinal structures and hence to alleviation of pain.

Selective sigma-1 receptor antagonists for the treatment of pain.

The sigma-1 receptor (σ1R) is located in areas of the CNS key for pain control and belongs to a unique target class with chaperoning functions over different molecular targets involved in transmission and amplification of nociceptive messages. Preclinical evidence supports a role for σ1R antagonists in the treatment of pain states where hypersensitivity develops as hyperalgesia and allodynia, two common symptoms encountered in neuropathic and other chronic pain conditions. Additionally, σ1R antagonists increase opioid analgesia without increasing opioid-related unwanted effects, which point to their potential use as opioid adjuvant therapy. This review summarizes the structure and function of the σ1R as well as the medicinal chemistry and pharmacological studies directed to the identification of σ1R antagonists for the treatment of pain.

Chemokines and attraction of myeloid cells in peripheral neuropathic pains

Chronic neuropathic pain has become a real social issue, due to the difficulty of its treatment and by the major impairment to quality of life that it causes in every day behavior. Understanding neurobiological basis and pathophysiological causes of diverse painful syndromes constantly evolves and reports the complexity of its mechanisms. Unfortunately this complexity makes it difficult to discover effective treatments against chronic pain syndromes, in particular as regards peripheral neuropathic pains. Recent studies reveal that, during chronic peripheral neuropathy, inflammatory mediators (in particular chemokines), besides their implications in the modulation of nociceptive messages and central neuroinflammatory mechanisms, play a critical role in the orchestration of the immune response induced by a peripheral nerve lesion. In this review, after a brief introduction about chemokines and their role in neuromodulation of the nociceptive message, we will attempt to define their functions and implications in the immune response associated to peripheral neuropathies. Thus, perfectly understanding the molecular and cellular communications between the nervous system and the immune system will be useful for the future development of novel and innovative therapeutic strategies against these highly disabling pathologies.

Noxious stimulation excites serotonergic neurons: A comparison between the lateral paragigantocellular reticular and the raphe magnus nuclei

The present study was designed to record electrophysiological responses to graded noxious thermal stimuli of serotonergic and nonserotonergic neurons in the lateral paragigantocellular reticular (LPGi) and the raphe magnus (RMg) nuclei in rats. All of the neurons recorded were juxtacellularly filled with neurobiotin and identified with double immunofluorescent labeling for both neurobiotin and serotonin. Under halothane anesthesia (0.75%), noxious thermal stimuli ⩾48°C activated almost all (88%) of the serotonergic neurons located within the LPGi (n=16). The increase in firing was clear (3.4±0.3spike/s: mean of responses above the population median) and sustained during the whole application of strong thermal noxious stimuli, with a high mean threshold (48.3±0.3°C) and large receptive fields. Recording of serotonergic neurons in the RMg (n=21) demonstrated that the proportion of strongly activated (>2spike/s) neurons (19% vs 59% for the LPGi) as well as the magnitude of the activation (2.1±0.4spike/s: mean of responses above the population median) to thermal noxious stimuli were significantly lower than in the LPGi (P<.05). Within the boundaries of both the LPGi and the RMg (B3 group), nonserotonergic neurons were also predominantly excited (75%) by noxious stimuli, and the resulting activation (7.9±1.2spike/s) was even greater than that of serotonergic neurons. Thermal noxious stimuli–induced activation of LPGi serotonergic cells probably plays a key role in serotonin-mediated modulations of cardiac baroreflex and transmission of nociceptive messages occurring under such intense noxious conditions.

Anatomophysiologie des douleurs pelvipérinéales chroniques

To determine the mechanisms involved in the regulation of pelvic and perineal pain. Description of the anatomical pathways mediating nociceptive transmission and the physiological mechanisms of pain control. The pelvis and perineum do not have the same innervation. The pelvis is innervated by the sympathetic nervous system, while the perineum is innervated by the somatic nervous system via sacral nerve roots (and the pudendal nerve) and the thoracolumbar sympathetic nervous system. Systems of regulation of nociceptive messages are present at all levels of the nervous system. Two of these systems are essential: one situated in the dorsal horns of the spinal cord (gate control) and another supraspinal system (descending inhibitory system). Via a series of filters and amplifiers, the nociceptive message is integrated and analysed in the cerebral cortex, with interconnections with various areas, especially involving memory and emotion. Excessive nociceptive stimulation must be clearly distinguished from dysfunction of pain control systems (for example neuropathic pain). The definition of pain: "unpleasant sensory and emotional experience related to a real or potential tissue lesion or described in terms of such a lesion" clearly indicates that not all pain is inevitably related to a persistent and visible cause. Convergence phenomena identified between nerve pathways of the various systems and pelvic organs account for the possible diffusion of visceral nociceptive messages and interactions between organs. A good knowledge of anatomy is essential to understand the patient's description of the pain, and a good knowledge of the modalities of pain control is essential to correctly adapt treatment strategies (drugs, neurostimulation, psycho-behavioural therapy, etc.).

Les infiltrations du système nerveux sympathique dans la prise en charge thérapeutiques des douleurs pelvipérinéales chroniques

The autonomic sympathetic nervous system conveys nociceptive messages from the viscera to the brain. The purpose of this article is to review the place of autonomic nerve blocks in the management of chronic pelvic and perineal pain. A comprehensive review of the literature was performed by searching PubMed for articles on autonomic nerve blocks and related procedures in the management of chronic pelvic and perineal pain. Intervention on the sympathetic nervous system for the management of chronic pelvic and perineal pain has been proposed at main three levels: ganglion Impar, hypogastric plexus and L2 lumbar sympathetic blocks. Infiltration of the sympathetic nervous system with local anaesthetic constitutes a diagnostic test by providing pain relief for the duration of action of the local anaesthetic in two third of patients. Specific procedures have been performed such as alcohol nerve block, radiofrequency ablation, surgical section or botulinum toxin infiltration at these various sites to achieve more lasting results. A sympathetic nervous system test block plays a diagnostic role in the management of chronic pelvic and perineal pain by guiding more specific global pain management procedures.

Définitions, classifications et lexique des douleurs pelvipérinéales chroniques

To review the definitions and classifications of chronic pelvic and perineal pain and to describe the concepts of chronic pelvic and perineal pain syndrome and the global diagnostic and aetiopathogenic approach. A review of the literature was performed by searching the Medline database (National Library of Medicine). Search terms were either medical subject heading (MeSH) keywords (classification, complex regional pain syndrome, fibromyalgia, myofascial pain syndrome, neuralgia, pelvic pain, postoperative pain, prostatitis, referred pain, syndrome) or terms derived from the title or abstract. Search terms were used alone or in combinations by using the "AND" operator. The literature search was conducted from 1990 to the present time. Chronic pelvic and perineal pain does not only consist of symptoms localized to an anatomical region present for 3 to 6 months, but also constitutes a distinct, complex, multidimensional disease entity, comprising psychological, organic and psychosomatic phenomena, called chronic pelvic and perineal pain syndromes. These syndromes are responsible for disability, impaired quality of life, and induce considerable health care consumption and sick leave. They alter the patient's personality and affect his or her behaviour, sex life, family life, social life and work life. The usual clinical approach to these syndromes, looking for an organ or tissue disease responsible for pain, is negative. The approach to this type of pain must be much more global and consists of looking for disturbances of the regulation of pelvic and perineal nociceptive messages and dysfunction of the organ or structure concerned. The current definitions and classifications of chronic pelvic and perineal pain comprise the concepts of syndrome, functional disease and global approach and differ from the strict organ-based context and the classical medical approach (infectious, inflammatory, metabolic, endocrine) in order to focus pain syndromes on the pain itself and the associated symptoms.