ITALY: FS Italiane President Gianluigi Castelli announced that the group was investing €6bn in new regional trains at the launch of two types of rolling stock at InnoTrans. In the ‘biggest-ever’ fleet renewal programme, FS would receive 600 trains by 2023, with deliveries running at nine sets per month and a target of 13 a month in the future.Italian Minister of Infrastructure and Transport Danilo Toninelli underlined the environmental importance of rail travel and stressed the need to invest in regional and commuter services. The two trains are the single-deck ETR103, part of Alstom’s Coradia Stream family branded ‘Pop’by Trenitalia, and the double-deck ETR521 high-capacity EMU built by Hitachi Rail Italy to its Caravaggio design and branded ‘Rock’ by Trenitalia. Director General of FS Italiane Gianfranco Battisti said that the new trains would enter service from May 2019 as part of a rolling stock renewal programme ‘without precedent’ in the history of Italian railways.Managing Director of Hitachi Rail Italy Alistair Dormer said that the Rock was the first train that his company had designed and built in Italy for Italy and was at ‘the cutting edge of technology’.Henri Poupart-Lafarge, President and Managing Director of Alstom highlighted the environmental advantages of the Coradia Stream, noting that the Pop would consume 30% less energy than the previous generation of regional trains.
This time of year, dry weather and cooler temperatures typically keep mosquito populations low in Palm Beach County. However, weather systems that recently moved through the area have caused unusually high mosquito populations to develop, prompting the county’s Mosquito Control Division to conduct an unprecedented December spray program.The weather system’s accompanying high winds have complicated matters by preventing the use of aerial spraying as wind speeds have exceeded the legal application limit. Aerial spraying requires a narrow range of wind conditions, between 2 mph and 10 mph, to effectively reduce mosquito populations. In the meantime, spraying will be conducted by trucks, and crews will be working in areas with the most severe mosquito activity in the county.Aerial spraying will resume delivering wide-area relief as soon as wind conditions allow, perhaps over the holidays. We ask that the residents of areas plagued with mosquitoes be patient while all efforts are made to deliver mosquito control services to these areas.To further help control mosquitoes, residents are asked to drain or minimize standing water on their properties.
FIRST SERVE PERCENTAGENadal – 58Millman – 68PERCENTAGE OF POINTS WON ON FIRST/SECOND SERVENadal – 80/56Millman – 63/36TOTAL POINTSNadal – 93Millman – 70 Nadal, a three-time champion at Flushing Meadows, improved to 15-0 in first-round matches in New York.The Spanish second seed will face another Australian, Thanasi Kokkinakis, in the second round. Related News U.S. Open 2019: Carlos Ramos not umpiring me? ‘I don’t know who that is,’ Serena Williams says U.S. Open 2019: Coco Gauff, 15, battles into second round U.S. Open 2019: Roger Federer fends off Sumit Nagal in New York test Rafael Nadal maintained his perfect first-round record at the U.S. Open, cruising past John Millman on Tuesday.The 18-time grand slam champion was untroubled by Australian Millman, easing to a 6-3, 6-2, 6-2 victory on Arthur Ashe Stadium. Staring at the second round like… @RafaelNadal sprints past John Millman 6-3, 6-2, 6-2. | #USOpen pic.twitter.com/7CN1vxrHCs— ATP Tour (@ATP_Tour) August 28, 2019After a grueling start featuring numerous long exchanges, Nadal broke for 3-1 when Millman — trying to be aggressive — sent a forehand long.Not even a time violation when serving for the set could slow down Nadal, who closed out the opener.While not at his best, Nadal looked comfortable and he broke in the fifth game of the second set, forcing Millman into an error with a brilliant forehand down the line.Nadal eased through the second set and made the perfect start to the third, breaking in the opening game after another big forehand.Millman stunned Roger Federer on his way to the U.S. Open quarterfinals last year, but he was no match for a typically relentless Nadal, who powered through. STATISTICAL BREAKDOWNRafael Nadal  bt John Millman 6-3 6-2 6-2WINNERS/UNFORCED ERRORSNadal – 21/31Millman – 17/22ACES/DOUBLE FAULTSNadal – 6/3Millman – 4/0BREAK POINTS WONNadal – 5/15Millman – 0/3
By JARROD POTTER BALWYN had answers to every Noble Park question – downing the Bulls 17.14 (116) to 11.10 (76)…[To read the rest of this story Subscribe or Login to the Gazette Access Pass] Thanks for reading the Pakenham Berwick Gazette. Subscribe or Login to read the rest of this content with the Gazette Digital Access Pass subscription.
Nelson Youth Soccer U14 Selects have been on a bit of a run of late, capturing a pair of medals on the Girl’s Rep Soccer Tour. The Reps recently defeated city rivals U13 Selects to capture the gold medal at the Terry Walgren Girl’s Soccer Tournament Sunday at the Lakeside Pitch.Previously, the Selects earned a silver medal in Coeur d’ Alene.Staff and management at Mallard’s Source for Sports would like to honour the Selects with Team of the Week accolades.The team includes, back row, L-R, coach Paul Burkart, Allie Zondervan, Lakpa Dietz, Natanya Hanley, Isabelle Morley, Naomi Perkins, Kyra Burkart, Camille Gebhart and coach Pat Perkins.Front, Emma Gregorich, Maya Mierau, Darian Voisard, Merissa Dawson, Bronwyn Sutherland, Maddy Sternloff, Amelia Martzke, Emily Graeme and goalkeeper Haley Cooke. Missing, Kali Horner, Emma DeCosta and Morgan Livingston.
The Nelson Leafs are busy gearing up for next season by making a few roster moves.Leafs management have acquired two players while sending another off to North East Alberta.Wednesday, the Leafs traded the playing rights of forward Tyler Nypower to the St. Paul Canadiens of the North Eastern Alberta Junior B Hockey League in exchange for a development fee.Nypower was a key cog in the Leafs offence last season, finishing fourth in team scoring with 12 goals and 26 assists for 38 points in 38 games for Nelson. The six-foot, 165 pound forward, who came to Nelson from Columbia Valley Rockies, added three goals and two assists in 10 playoff games for the Leafs.Earlier in the week, Nelson acquired two Nelson Minor Hockey products, goalie Curt Doyle and Tyler Badger in separate deals with Castlegar Rebels and Osoyoos Coyotes.Doyle, a 20-year-old netminder, and Badger, a 16-year-old forward, both came to Nelson in exchange for development fee.Doyle, who played five games in 2016 for Nelson, has been part of the Rebels goaltending team for the past three seasons, finishing with 3.91 goals against average in 2019.Badger was picked up by the Coyotes following a season with the Okanagan Hockey Academy.In 47 games last season for Osoyoos, Badger scored 10 goals while adding 13 assists for 23 points.The Nelson Leafs begin the 2019-20 season in August with its Main Training Camp at the NDCC Arena.
MAURICIO POCHETTINO has congratulated Harry Redknapp for being crowned King of the Jungle – and claimed his victory as silverware for Tottenham.Redknapp has become a nationwide hit after making a huge impact on I’m A Celebrity, Get Me Out Of Here.2 Harry Redknapp was crowned King of the Jungle – a trophy Mauricio Pochettino claimed for TottenhamCredit: Rex FeaturesThe 71-year-old former Spurs manager won the ITV reality show on Sunday night on the back of his impressive showing in Australia.And though he knew little about what happened Down Under, Redknapp’s triumph was more than enough for Pochettino to claim the end of Tottenham’s decade-long wait for silverware.Spurs boss Pochettino said: “He won? Congratulations to Harry.”One trophy for us. At least.”2 Mauricio Pochettino says Redknapp winning I’m A Celeb can go down as a trophy for SpursCredit: AP:Associated PressPochettino’s failure to lead Spurs to any silverware during his time with the club has seen much scrutiny put on his players and his leadership.For all their impressive performances, nurturing a young squad on to become one of the best in England, there is nothing to show for it.The last time Tottenham tasted victory in a major competition came in 2008 when they won the League Cup.Pressure has been growing on the club to win something given the riches of talent they currently have in the squad.BRO MESSAGEBobby Charlton’s touching tribute to Jack revealed as he misses funeral serviceFRESH OUTFITMicah Richards pokes fun at Roy Keane backstage at Sky Sports studiosFALL OF TROYDeeney calls Sky reporter ‘cheeky b******’ after he asks about retirementSHOTS FIREDDenis Irwin’s son trolls Liverpool fans with savage Steven Gerrard tweetPicturedC’MON THE LADSRamos’ becomes dad again as wife gives birth to FOURTH son Maximo AdrianoVideoROY MEANKeane says ‘that’s why they never win anything’ as Villa celebrate staying upPicturedHARRY’S HEROES Kane says goodbye to Tottenham team-mates Vertonghen and VormRED LETTER DAYKeane and Neville urge Man Utd to invest big after securing Champions LeagueLive BlogUNITED LATESTMan Utd transfer news LIVE: All the gossip and updates from Old TraffordGREAT SCENERonnie Whelan celebrates with grandson as Liverpool lift Premier League trophyAnd only when they do manage to make that step will they be able to silence the critics who believe Spurs lack the killer instinct needed for success.But Pochettino can at least see the funny side of the situation – though clubs like West Ham and Portsmouth may also view Redknapp’s success as down to them.Harry Redknapp says his ‘scrubbed up’ I’m A Celebrity pal Emily Atack ‘looks very useful’ as he’s asked about her chances with son Jamie but when he saw her in the jungle he thought ‘you haven’t got a prayer!’
11 February 2009 Efforts to review the forensic and investigative capacity of the South African Police Service are already under way, and together with enhanced technologies would give a welcome boost to the country’s fight against crime, he said during his 2009/10 Budget speech to Parliament in Cape Town on Wednesday. Finance Minister Trevor Manuel on Wednesday announced a R5.4-billion allocation for the overhaul of South Africa’s criminal justice system. Funding is also provided for additional policing capacity during the 2010 Fifa World Cup, for building new prisons and for implementing the Child Justice Bill. Source: BuaNews In his state of the nation address on Friday, President Kgalema Motlanthe said that crime remained a major source of insecurity for South Africans. “Daily experience, in poor and affluent neighbourhoods alike, is one of apprehension at the possibility of violent attack.” South Africa’s crime situation, Motlanthe said, pointed to weaknesses in building the bonds of community solidarity, weaknesses in the criminal justice system – from investigation of crimes to rehabilitation of offenders – as well as weaknesses in the efficiency of the court system, both in terms of technical and other infrastructure and management. The funds will also go towards increasing the number of police officials from 183 000 in 2008/09 to over 204 000 in 2011/12. Motlanthe said that while South Africa’s overall crime rate, having peaked in 2002, had consistently declined since then, it was still not dropping fast enough. “The fact that incidents of violent robberies in households and businesses have been on the increase, and crimes against women and children have not abated in any significant measure, is a matter of great concern,” he said during the opening of Parliament. “A further R5.4-billion is allocated to interventions aimed at improving criminal justice services, the creation of an integrated fingerprint and DNA database, improving detective capacity, [and] upgrading IT and telecommunications systems,” Manuel said.
16 September 2013 Norway-based Scatec Solar announced on Monday that it had completed its 75-megawatt solar photovoltaic (PV) power plant in Kalkbult in the Northern Cape three months ahead of schedule, making it first project under South Africa’s renewable energy programme for private producers to be grid connected and operational. Scatec Solar was one of 28 independent power producers that signed contracts with the government late last year, in the first round of a programme that will see an initial 1 400 megawatts (MW) of renewable energy being added to South Africa’s energy mix, while bringing an estimated R47-billion in new investment into the country. The Department of Energy aims to bring 17 800 MW from renewable sources online by 2030. Scatec Solar has been awarded three projects with total capacity of 190 MW under the government’s programme. Construction of its next two projects, located in the Northern and Eastern Cape, has started and completion is expected by the middle of next year. The completed Kalkbult plant consists of more than 312 000 solar panels mounted on 156 kilometres of substructure, inverters, transformers and a sub-station. Kalkbult’s electricity will be sold to state company Eskom through a 20-year purchase agreement. According to Scatec Solar, the annual production of 135-million kWh will cover the electricity demand of 33 000 households, while reducing the country’s carbon dioxide emissions by almost 115 000 tons per year. “The South African authorities are committed to implementing an ambitious renewable energy programme, and we find great satisfaction in being able to contribute to its success through our own projects, which we have actively been developing in South Africa over the last four years,” Scatec Solar CEO Raymond Carlsen said in a statement on Monday. “This country boasts some of the best conditions for solar power in the world, and the annual output of 135-million kWh produced at the Kalkbult plant will benefit both the region and the local community in which we operate.” SAinfo reporter
As prescribing skyrocketed, so did overdoses. U.S. deaths from prescription opioids have roughly quadrupled in the last 2 decades, reaching 21,000 in 2014. Making things worse, abundant prescription opioids have been diverted for recreational use, which has driven up rates of heroin addiction as users have sought cheaper or more accessible alternatives. Both prescription and illegal opioids kill when high doses slow breathing, especially when combined with alcohol or antianxiety drugs called benzodiazepines. “I’m not sure you could find an example of physicians doing more harm to human beings than we have achieved in our liberal opiate prescribing,” says David Clark, an anesthesiologist at Stanford.Mao and others wondered whether hyperalgesia was another important opioid side effect. People might be seeking a higher dose as drug-induced pain compounded the original pain, he thought. If so, doctors who ignore hyperalgesia might bump up the dose when the right decision was to reduce it. And when a patient tried to taper off a drug, a temporarily lowered pain threshold might make it harder for them to manage without it. “If they’re hyperalgesic, they can just go back to the drug again to feel okay,” says Jose Moron-Concepcion, a neuroscientist at the Washington University School of Medicine in St. Louis in Missouri. The evidence for hyperalgesia is clearest in people taking extreme doses—for instance, in opioid abusers or terminal cancer patients managing severe pain. Surgical patients given large amounts of the opioid remifentanil have shown signs of hyperalgesia; they have larger areas of soreness around their wounds and seem predisposed to chronic pain following surgery. But what about patients who take lower doses of opioids daily over months or years to manage chronic pain? As a pain specialist at a large teaching hospital, Mao frequently encounters patients who can’t find relief from increasing opioid doses and who tell him that their pain has become worse—diffuse, nagging, and harder to pinpoint.But just how many people experience OIH, and at what opioid dose, is hard to say. The phenomenon can be very hard to distinguish from tolerance, when pain increases as the drug loses its effectiveness over time. (It’s also possible that a patient’s underlying condition has changed, or that the chronic pain itself has kicked their pain signaling into high gear.)Because diagnosing hyperalgesia can be a guessing game in the clinic, some researchers have turned to the lab. They have tried to document changing pain thresholds with quantitative sensory tests, like the so-called cold pressor test Hutchinson witnessed in the methadone patients in Australia, or contraptions that apply heat or pressure to the skin. But the studies have been small and the results inconsistent. “Nobody has actually shown that that particular stimulus in a human being is a valid way to say, ‘Yes, this person has become hyperalgesic,’” Angst says. In 2001, researchers at the Chinese Academy of Sciences in Shanghai reported that chronic morphine administration in rats activated glial cells called astrocytes in the spinal cord. Subsequent studies showed that inhibiting the inflammatory molecules released by glia could reverse hyperalgesia and tolerance in the rats. The results suggested that opioids may trigger glia to set off system-wide pain signaling that both counteracts the pain relief from the drug and makes the body generally more sensitive to pain.Many see dampening this inflammatory response as a promising way to fight hyperalgesia, because it would not interfere with opioids’ pain-relieving activity on neural receptors. Several efforts are underway. The San Diego, California–based biotech company MediciNova recently completed a phase II trial of a glia-inhibiting drug called ibudilast, already approved as an asthma treatment in Japan, to relieve pain and treat withdrawal in opioid abusers. A study led by researchers at Yale University is testing the antibiotic acne medication minocycline, which is also thought to block glial activation in the brain. And research spun out of neuroscientist Linda Watkins’s group at the University of Colorado in Boulder is testing a new pain drug that may tame glia in the spinal cord by blocking a signaling protein on their surface.If inflammation turns out to be a key driver of OIH, it might also point the way to a better test for the effect, says Lesley Colvin, a pain researcher at the University of Edinburgh. Markers of inflammation in the blood might correlate with clinical signs of hyperalgesia or declining pain thresholds on sensory tests. Colvin says she already sees strong evidence of hyperalgesia in high-dose opioid users at the clinic where she works. With so much at stake, she is eager to understand the phenomenon and how it might affect them long term. “Although it’s complicated,” she says, “that doesn’t mean we shouldn’t try and work out the details.” V. Altounian/Science Martin Angst, anesthesio logist and clinical pharmacologist, Stanford University Turning down the volume Animal studies have revealed several ways in which opioids may amplify pain signals in the central nervous system, suggesting targets for drugs that could counter the effect. Some studies of hyperalgesia rely on gradually heated probes applied to the skin. By Kelly ServickNov. 3, 2016 , 2:00 PM In 2006, for instance, a team that included Angst and Clark gave the cold pressor test to six people with chronic lower back pain before and after a monthlong course of morphine pills. After the drug treatment, the team found signs of hyperalgesia: On average, the subjects registered pain from the ice water about 2 seconds earlier, and removed their hands about 8 seconds earlier, than they had beforehand. But those results didn’t hold up in a larger group of 139 patients randomized to take opioids or placebo, nor did they appear in a different pain test that applied a gradually heated probe to the forearm. Then in 2013, a study with a different methodology seemed to confirm the effect. A research team in Israel reported evidence of hyperalgesia in 17 of 30 patients with radiating spinal nerve pain by asking them to rate the intensity of heat pain on a numerical scale before and after a 4-week course of hydromorphone. If you can’t reliably diagnose hyperalgesia, it’s hard to predict its long-term effects, says Michael Hooten, an anesthesiologist at the Mayo Medical School in Rochester, Minnesota. His group found evidence in 91 patients tapering off opioids that those whose doses were higher at the start, forcing them to make greater reductions over the 3-week program, had worse measures of heat pain hyperalgesia. But the team wasn’t able to track these patients long-term to ask the bigger questions: How long until their pain thresholds bounced back to normal? Do hyperalgesic patients who manage to quit taking opioids ultimately see improvements in pain? Are hyperalgesic patients more or less prone to addiction or relapse?For some, this lack of evidence makes research into hyperalgesia look like a dead end. “When I go to work every day, I don’t think about opioid-induced hyperalgesia,” says Gary Bennett, a pain researcher at the University of California in San Diego. “We know that it’s real. We don’t know how important it is, and it’s really, really hard to answer that question, so let’s move on.” Related Article Could pot help solve the U.S. opioid epidemic? Why painkillers sometimes make the pain worse Your biology fights back and says, ‘I’m blindfolded to pain by all these chemicals. I need to be able to sense pain again.’ Matthew Rakola Paradoxical as it may seem, OIH makes evolutionary sense. “Nature didn’t come up with pain just to torture mankind,” says Martin Angst, an anesthesiologist and clinical pharmacologist at Stanford University in Palo Alto, California. Pain causes us to recoil from a hot stove and to stay off an injured leg while it heals. And when it’s crucial that we temporarily ignore pain—say, when we run on that injured leg to evade a charging lion—the body has a way of numbing it, in part by releasing its own opioids. These natural molecules bind to receptors on neurons to block pain signals and activate reward centers in the brain. But doses of prescription opioids are orders of magnitude higher than our endogenous levels, Angst says. Confronted by these, “your biology fights back and says, ‘I’m blindfolded to pain by all these chemicals. I need to be able to sense pain again.’”Mao was among the first to delve into potential mechanisms of OIH in an animal model. In 1994, while at Virginia Commonwealth University in Richmond, he and his colleagues showed that after 8 days of spinal morphine injections, rats were quicker to pull their paws away from a gradually heated glass surface. The animals’ baseline pain threshold had changed, and the effect was something more than tolerance, in which the body requires increasing doses of a drug to get the same effect. In this case, a higher dose could actually increase sensitivity to pain. The researchers found they could reverse the hyperalgesic effect by blocking certain receptors on neurons in the animals’ spinal cord. These N-methyl-D-aspartate (NMDA) receptors pick up chemical signals—notably an excitatory molecule called glutamate—released by sensory neurons projecting from the skin and organs, and transmit pain signals up to the brain. Researchers already knew that even without opioids, some people with chronic pain from nerve damage or fibromyalgia, for example, experience hyperalgesia when normal pain signaling gets reinforced and amplified over time. It appeared that, at least in animals, opioids had a similar effect.By 2000, Mao was turning his attention to patients, and the population of opioid users was expanding. Doctors had begun to consider the drugs relatively safe options for managing chronic pain. With the release and aggressive marketing of the long-acting narcotic OxyContin in 1996, a class of drugs that had largely been reserved for cancer patients was becoming a go-to treatment for conditions such as lower back pain. Related Special Issue The future of pain research Mark Hutchinson could read the anguish on the participants’ faces in seconds. As a graduate student at the University of Adelaide in Australia in the late 1990s, he helped with studies in which people taking methadone to treat opioid addiction tested their pain tolerance by dunking a forearm in ice water. Healthy controls typically managed to stand the cold for roughly a minute. Hutchinson himself, “the young, cocky, Aussie bloke chucking my arm in the water,” lasted more than 2 minutes. But the methadone patients averaged only about 15 seconds.“These aren’t wimps. These people are injecting all sorts of crazy crap into their arms. … But they were finding this excruciating,” Hutchinson says. “It just fascinated me.” The participants were taking enormous doses of narcotics. How could they experience such exaggerated pain?The experiment was Hutchinson’s first encounter with a perplexing phenomenon called opioid-induced hyperalgesia (OIH). At high doses, opioid painkillers actually seem to amplify pain by changing signaling in the central nervous system, making the body generally more sensitive to painful stimuli. “Just imagine if all the diabetic medications, instead of decreasing blood sugar, increased blood sugar,” says Jianren Mao, a physician and pain researcher at Massachusetts General Hospital in Boston who has studied hyperalgesia in rodents and people for more than 20 years.Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)But how prevalent hyperalgesia is, and whether it plays a role in the U.S. epidemic of opioid abuse and overdose, is unclear. A lack of reliable testing methods and a series of contradictory papers have created believers and skeptics. A few researchers, like Mao, think hyperalgesia is an underappreciated puzzle piece in the opioid epidemic—a force that can pile on pain, drive up doses, and make it harder for chronic users to come off their drugs. Some of those researchers are looking for ways to turn down hyperalgesia, to help patients function on lower doses of their oxycodone, for example, or make it easier to taper off it altogether. Others see OIH as an oddity in the literature—real, and a powerful clue to the workings of pain pathways, but unlikely to tighten the grip of opioids on most patients. Hutchinson thinks the majority of physicians are either unaware of hyperalgesia or unconvinced of its importance. “I think if you surveyed prescribers of opioids, they would be divided probably 60–40.” Mao isn’t ready to move on. He believes the risk of hyperalgesia should motivate doctors to try tapering patients off their opioids when their pain worsens without an obvious cause. But in his experience, only about a third of chronic pain patients are willing to try that. So he’s hoping for a different solution: a drug that targets the mechanisms behind hyperalgesia and that might be given alongside an opioid, either when it’s first prescribed or when a doctor suspects OIH. Mao is recruiting patients for clinical trials to test two candidate drugs. One is ketamine, an anesthetic that blocks NMDA receptors. The other, guanfacine, is currently used to treat high blood pressure and is thought to keep sensory neurons from releasing glutamate into the spinal cord. A team led by Peggy Compton of Georgetown University in Washington, D.C., meanwhile, is investigating a pain and antiseizure drug called gabapentin that may block neural transmission to reduce excessive pain signals. Other groups are attacking opioid side effects, including hyperalgesia, from a very different angle. In the early 2000s, researchers began exploring the role of glia, star-shaped immune cells in the brain and spinal cord, which were traditionally thought to function as mere “housekeepers,” offering structural support for neurons and removing debris. But when the immune system becomes activated in response to an illness or injury, glia in regions associated with pain processing seem to take on another role: They release inflammatory molecules that interact with nearby neurons to amplify pain signals.